The cutting edge Sanjay Gupta In the joint Healing wounds Losing

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special report
INSIDE JOB
SURGEONS AT WORK
The cutting edge
The world of surgery evolves
Sanjay Gupta
CNN’s surgeon journalist
In the joint
Focusing on the gristle
Healing wounds
New techniques to repair the skin
Losing consciousness
What does it mean to go under?
Funky hats and
rock ‘n’ roll
My, how the OR has changed
plus
An excerpt
from the book
Surgeon General’s Warning
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RODIN’S VIRTUAL HANDS
ART AND MEDICINE
M E E T I N AU G M E N T E D R E A L I T Y
While James Chang, MD, was doing his surgery residency at Stanford, he took
to playing a game of sorts with the campus Rodin sculptures: He’d come up
with specific medical conditions based on the appearance of their hands. He
had plenty of hands to choose from as Stanford’s Cantor Arts Center holds
one of the world’s largest Auguste Rodin collections, with 200 of his sculptures,
including The Thinker and The Gates of Hell.
“I began to notice that most of the hands looked like the conditions I was treating, from fractures to
malformations to tumorous growths,” Chang says.
Rodin’s Large Left Hand appeared to have some broken metacarpals. He speculated that Large
Clenched Hand, a sculpture frozen in a painfully exaggerated and abnormal posture, had Charcot-MarieTooth disease, an inherited neurological disorder. From sculpture to sculpture, hand to hand, the surgeon
proceeded to identify a ganglion cyst, a thumb amputation, a stiff joint and other conditions.
When he became a surgery professor at Stanford, his hobby turned
into a teaching tool, which he incorporated into the undergraduate
course Surgical Anatomy of the Hand: From Rodin to Reconstruction.
Now Chang’s diagnoses are part of the inspiration behind an
exhibit at the art center, Inside Rodin’s Hands: Art, Technology,
and Surgery, celebrating the connection between Rodin’s fascination with the human form and medicine’s fascination with human
anatomy. The center’s program includes a “virtual operation” to
fix the perceived broken fingers on the Large Left Hand and a
3-D, augmented-reality model showing how the statue would look
post-surgery. The exhibit runs through Aug. 3.
Connie Wolf. “It’s unlike anything we’ve ever done before.”
Stanford has a history of scientists using art to inform their teaching and learning, stretching back at
least to the early 1990s, when surgery professor Robert Chase, MD, and Rodin authority Albert Elsen, PhD,
challenged medical students to find clues of medical conditions in the Rodin sculpture garden — located
conveniently near the medical school.
The new exhibit builds upon this history, says Paul Brown, DDS, consulting associate professor of anatomy.
Brown, together with exhibit production manager Matt Hasel and medical artist Sarah Hegmann, used CT scans
from Stanford hand clinic patients to create virtual sculptures showing the hands’ supposed internal anatomies.
Rodin studied anatomy like other art students of his day, and he spent time at the Musée Dupuytren in
Paris (a museum of anatomical items illustrating diseases and malformations), says Rodin expert Bernard
Barryte, the exhibit’s curator. So were Rodin’s hand sculptures based on living models or did they grow
from his imagination? According to Barryte, no one knows for certain. —
TRACIE WHITE
WE B E X T RA
See a video
about the
exhibit at http://stan.
md/1nxKnv9
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WI TH THE HELP of an iPad
at the Stanford exhibit, you can see
virtual blood vessels, nerves and
bones within Rodin’s Left Hand
of Eustache de St. Pierre.
“Art is informing medicine in the exhibit, and medicine is informing art,” says the museum’s director,
V O L U M E
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Inside the mind
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SPECIAL REPORT
Inside job
S U R G E O N S AT W O R K
6 Opening up By Ruthann Richter
T HE E VO LVI N G W O R L D O F S U R G E RY
14 Her left hand By Tracie White
A S U R G E O N ’ S JO U RN E Y B AC K
22 Medical coverage
A CO N VE R S AT I O N W I TH C N N ’S S AN J AY G U P TA, MD
24 Incredible cartilage By Sara Wykes
FO CU S I N G O N G R I S TL E I N TH E E F F O RT TO I MP RO V E J O I N T RE P L AC E ME NT S
28 Sculpting bones By Julie Greicius
Bones and bravery
page 28
A T E CHN I Q U E TH AT R E Q U I RE S P R E C I S I O N , ARTI S TRY AN D , F R O M TH E PAT IENT, T RUE GRIT
32 Healing wounds By Elizabeth Devitt
CL O S I N G T HE G AP
36 Going under By Sarah C.P. Williams
R E S E A R CH I N T O C O N S C I O U S N E S S C RO S S E S F RO M P H I L O S O P H Y TO S C I ENC E
40 In the groove By M.A. Malone
B E HI N D T HE S C E N E S I N TH E O R
PLUS
42 Rethinking Alzheimer’s By Bruce Goldman
L O O KI N G T O I T S O RI G I N S F O R A TR E ATME N T
46 The demise of the surgeon general By Mike Stobbe
C O V E R : M A X A G U I L E R A - H E L LW E G
When being insured
buys worse care
page 4
A M E R I CA’ S DO C TO R FAD I N G AWAY
D E PA R T M E N T S
Letter from the dean
Upfront 3
Backstory 54
2
As an otolaryngologist, I was used to patients who found their symptoms perplexing. The vestibular
system, my area of focus, controls balance and eye movements, and when it malfunctions strange things
happen. But this man’s condition had me perplexed as well.
Over the next months some other patients reported similarly odd symptoms. One man told me he got
dizzy when he sang in the shower. Another patient said she could hear the sound of her own eyes moving.
Some patients assumed the problem was psychological until their psychiatrist referred them to me.
What was the culprit? My hunch was that it had something to do with the small, curved tubes in the
inner ear that help us sense motion — the semicircular canals. I first tested my theory by observing these
patients’ eye movements in response to loud noises — a technique used over a century ago for
defining the relationship between each of the three semicircular canals and the eye movements
that result from their activation. I found that a canal was indeed involved in causing this bizarre
constellation of symptoms and signs: the superior semicircular canal.
When I explored further using the advanced imaging techniques of the day, I discovered
the patients had tiny holes in the bone overlying this canal. The openings allowed changes in
intracranial pressure or sound transmitted through the inner ear to cause motion of fluid in
the superior canal and that in turn led to the symptoms and the eye movements. I labeled the
openings with the word dehiscence and thus “superior canal dehiscence syndrome” entered the
medical vocabulary.
I was glad to have discovered the cause and manifestations of the syndrome, but what mattered most to me, and certainly to my patients as well, was figuring out how to treat it. So I was extremely pleased that the surgical procedure I devised alleviated my patients’ symptoms — and could be
used to reduce the suffering of hundreds of others.
In operating rooms today, patients benefit from spectacular innovation. Perhaps the most revolutionary change during my lifetime has been a shift toward minimally invasive surgery. Instead of traditional approaches, which often require large incisions and extensive manipulation of tissues and organs,
many surgeries are now accomplished through tiny entry portals. This low-impact approach to surgery
usually results in less risk of infection, less pain, less damage to tissues and faster recovery. Instead of a
week in the hospital for gall bladder removal, most patients can be back home the next day.
At Stanford Medicine, innovation is part of our culture, so it’s no surprise that we’re a hotbed for new
techniques and technologies that improve surgery results. Among recent advances: brain surgeries that
bypass easily damaged healthy tissue by using the nostril as an access route, tools for minimally invasive
surgeries sized to treat children, a retraction device that protects against wound infection and a postsurgical dressing that reduces scarring. The power of innovation in surgery continues to amaze me. It inspires me to push ahead with our
initiatives to transform the science and practice of medicine for a healthier world. It fills me with gratitude for the patients who enable innovation to move forward. And it explains why I’m so proud of
Stanford Medicine, where innovation flows freely.
Sincerely,
LLOY D B. MINOR, MD
Carl and Elizabeth Naumann Dean of the School of Medicine
Professor of Otolaryngology-Head & Neck Surgery
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GL EN N MATSUMUR A
letter from the dean
It was an office visit nearly 20 years ago, yet I remember the
April 1995 day as if it were yesterday. My patient was a 50-year-old man
with a strange problem: Whenever he whistled or hummed loudly,
objects seemed to him to move around “like on a clock face.”
upfront
A
Q U I CK
L O O K
AT
THE
LATEST
DEV ELOPMENTS
F ROM
S TANF ORD
From
smartphone to
“eyephone”
Garbage
strike
“THINK INSTAGRAM FOR THE
EYES,” says as-
Normally, the body is extremely efficient
at taking out the garbage. Two hundred
billion cells die every day in our bodies,
and most get cleared out within a matter
of seconds. But when this process breaks
down and garbage, in the form of dead
cells, starts building up in the walls of
blood vessels, it’s not a good thing.
Researchers led by Nicholas Leeper,
MD, assistant professor of cardiovascular
medicine and of vascular surgery, now
have evidence that faulty garbage disposal explains why variation in one particular stretch of chromosome 9 increases
risk for a wide range of cardiovascular
or necrotic cells are removed. Mice with
diseases, including stroke, heart attacks
this genetic variation showed an increase
and aneurysms.
in buildup of these dead cells, further ad-
Their research, published in the Jour-
vancing their atherosclerosis.
nal of Clinical Investigation, shows that
“If you were born with genetic varia-
disturbing the usual genetic sequence
tion at the 9p21 locus, your risk of heart
at chromosome location 9p21 leads old
disease is elevated, though we haven’t
cells and debris to build up in the walls of
understood why,” Leeper says. “This re-
blood vessels.
search gets at that hidden risk. You can
In studies with mice with atheroscle-
be a nonsmoker, be thin, have low blood
rosis, the researchers showed that this
pressure and still be at risk for a heart
genetic variation leads to impaired “ef-
attack if you were born with this variant.
ferocytosis” — from the Latin for “take to
This work may help explain that inherited
the grave” — the process by which dead
risk factor, and more importantly help
HAR RY CA MPB ELL
MED IC INE
15
%
is the portion
of U.S. foreign
aid spent
to support
health. More
at http://stan.
md/1ieLGdU.
sistant professor
of ophthalmology
Robert Chang, MD.
His team has created inexpensive
adapters that make
it easy to use a
smartphone to capture high-quality
images of the eye
— one for the front
surface of the eye,
another for
the inside view.
It matters
because the
usual eye-imaging
instruments are expensive and hard to
use, and even ophthalmologists who
have the equipment
and know-how
find capturing and
sharing the images
slow going.
Physicians
who’d like to test
the adapters can
e-mail the team at
eyegotech@gmail.
com. — ROSANNE
SPECTOR
develop a new therapy to prevent the
heritable component of cardiovascular
disease.” — TRACIE WHITE
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Insult to injury
Have insurance, will get proper care? Maybe not, according to a
School of Medicine study. • In this study of cases of severe injuries, patients with insurance are more likely to get poor trauma
care than those without. Apparently, more insured patients are
held back at non-trauma hospitals instead of being sent to cen-
Mysterious
paralysis
SOFIA JARVIS WAS ONLY 2 YEARS OLD
WHEN, AS SHE REACHED
her left arm abruptly
stopped working. An MRI showed
a spinal cord lesion, and an
evaluation at Lucile Packard
Children’s Hospital Stanford
confirmed that she is among 16
children in California who
have developed sudden-onset,
permanent paralysis similar
to polio.
“Although poliovirus has been
eradicated from most of the globe,
other viruses can also injure the
spine, leading to a polio-like
syndrome,” says pediatric
neurologist Keith Van Haren, MD,
who diagnosed Sofia.
Doctors at the California Department of Public Health suspect
enterovirus-68, a member of the
poliovirus family, in cases like
Sofia’s, though they’re also
considering non-infectious causes.
The group of cases, which began
in mid-2012 and apparently
ended in late 2013, is similar to
recent outbreaks of paralysis from
another virus, enterovirus-71,
in Asia and Australia.
“Fortunately, this is not exceptionally virulent,” Van Haren says.
“It’s just happening in the very
unlucky few.”
But public health officials are
keeping a close watch on the
situation.
Meanwhile, Sofia, now 4, is generally healthy, but her arm is still
paralyzed. “We really want to know
what caused this,” says her mother,
Jessica Tomei. — ERIN DIGITALE
The findings of the study — one of the first such populationwide analyses — are concerning, the authors say.
•
Perhaps
emergency doctors fail to follow guidelines or recognize conditions that need extra care, suggests lead author Kit Delgado,
MD. Or maybe, more disturbingly, non-trauma hospitals hold
insured patients back so they can get reimbursed.
•
To curb
such practices, these hospitals could better monitor emergency
room encounters and split transfer costs with trauma centers,
the authors say. Previous studies show that trauma-center care
reduces the chances of a severely injured patient dying by 25
percent. • Senior author Nancy Wang, MD, earlier found such insurance-based disparities in trauma care access for children and
seniors in California. “Researchers and the community should
understand this trend,” she says, “so that it can be changed.”
• The
authors analyzed over 4,500 nationwide reported trauma
cases for the study. Next they hope to figure out if and how
patients’ preferences and knowledge of options affect trauma
transfer decisions. • Wang is an associate professor of surgery.
Delgado is a former Stanford emergency medicine instructor,
now at the University of Pennsylvania. — RANJINI RAGHUNATH
Short home videos
may become a
powerful tool for
diagnosing autism,
according to new
findings from associate professor
Dennis Wall, PhD,
and colleagues.
Wall’s team
scored the level
of autistic-type
behaviors in brief
YouTube videos of
100 children. The
method, described
April 16 in PLOS
ONE, identified
autism with 97
percent accuracy.
Though videobased diagnosis
won’t likely replace
traditional assessments, it could
speed the nowsluggish diagnostic
process. “We could
use this system for
clinical triage, as
a way to channel
traffic so that children can get the
kind of attention
they need as early
as possible,” Wall
says. Children who
clearly have autism
might be diagnosed
with videos and
started on therapy,
freeing clinicians
to spend more time
evaluating kids
whose condition is
less clear cut.
— ERIN DIGITALE
HAR RY CA MPB ELL
upfront
FOR A TOY,
ters specializing in trauma, the JAMA Surgery study reveals. •
AUTISM:
VIDEO
DIAGNOSIS
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The gene team
Samples’
side effects
There’s no such
thing as a free
lunch. Or, for that
matter, a free drug
sample. Oh, sure,
your doctor might
hand you a medication to try before
writing a prescription, and you could
walk out the door
without forking
over any cash. But
a recent study in
JAMA Dermatology
by Stanford dermatologist Alfred
Lane, MD, indicates
that when doctors
with access to
free samples do
write prescriptions,
they tend to be for
more-expensive
medications — an
average retail cost
of $465 versus
about $200 for a
diagnosis of adult
acne. Dermatologists without
access to samples
(Stanford for
example, bars doctors from receiving
drug samples) are
more likely to use
cheaper, generic
medications. Lane’s
not suggesting
your doctor’s
in cahoots with
pharmaceutical
companies — the
increased expense
is likely unintentional. What he’s
found is evidence
of the power of
marketing. And
the fact that your
mother is always
right. — KRISTA
Detection without
radiation
After learning they have cancer, lymphoma patients usually get
scans to locate tumors throughout their bodies. But the standard
imaging method, whole-body PET-CT, has a big drawback: One
scan exposes the patient to as much ionizing radiation as 700
chest X-rays. • This is especially risky for children and teenagers,
who are particularly vulnerable to radiation because they are
growing. They are also more likely than adults to live long enough
afterward to develop a secondary cancer. • That’s why researchers
One wholebody PET-CT
scan exposes
you to as
much ionizing
radiation as
700
chest X-rays.
CONGER
at the School of Medicine and Lucile Packard Children’s Hospital
Stanford developed an imaging technique that uses no radiation
at all. The method, described in The Lancet Oncology, is a modification of magnetic resonance imaging that employs a novel
contrast agent.
•
The new agent consists of injected nanopar-
ticles of iron, which are already FDA-approved to treat anemia.
On MRIs, they cause blood vessels to appear brighter, providing anatomic landmarks. The nanoparticles also cause healthy
tissues such as bone marrow, lymph nodes, liver and spleen to
appear darker, making tumors stand out.
•
The nanoparticle-
enhanced scans had similar levels of sensitivity, specificity and
diagnostic accuracy to whole-body PET-CT. Although more evidence of the technique’s efficacy is needed before it will be adopted, there are no technologic hurdles to its use. • “It’s really
Stanford’s
hospitals have
launched a new
testing service for
their patients that
deciphers their
DNA. The clinical
genomic service
will help doctors at
Stanford Hospital & Clinics and
Lucile Packard
Children’s Hospital
Stanford diagnose
and treat genetic
conditions. With
this, Stanford joins
a small group of
medical centers
— about 15 — that
provide genome
sequencing.
During its pilot
phase, testing will
be limited to patients with inherited cardiovascular
or neurological
disease, hereditary
cancer risk, unexplained drug reactions or an illness
that has defied
diagnosis. Its directors are Euan Ashley, MCRP, DPhil,
associate professor
of medicine and of
genetics, and Jason
Merker, MD, PhD,
assistant professor
of pathology.
In 2010, Ashley
and bioengineering
professor Stephen
Quake, PhD, were
the first in the
world to use a
healthy person’s
genome sequence
to predict disease
and anticipate
reaction to several
common medications. These new
genomic services
are the first wave
to test this new
knowledge. — SARA
WYKES
exciting that this will soon be clinically applicable,” says radiolo-
gist Heike Daldrup-Link, MD, who led the research. — ERIN DIGITALE
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Surgeons at work
O P E N I N G
U P
T H E E V O LV I N G W O R L D
OF SURGERY
S E P I D E H G H O L A M I STO O D AT T H E S U R G E O N ’ S E L B OW, U S I N G A M E TA L P R O N G TO E X P O S E T H E DA R K , T E N N I S B A L L
O F A T U M O R I N T H E YO U N G PAT I E N T ’ S CO LO N . I T WAS H E R T H I R D Y E A R AT STA N FO R D M E D I C A L S C H O O L , A N D S H E ’ D
B E E N A R E LU C TA N T ST U D E N T O F S U R G E RY, AS T H E O P E R AT I N G R O O M S E E M E D L I K E A N A L I E N , FO R E B O D I N G P L AC E .
But in her first week at Kaiser Permanente Santa Clara Medical Center, she was taken in by the artistry of the process — the ritual
passing of the instruments and the deft movements of the surgeon’s hands as he carefully cut out the cancer. There was a rhythm
to it. It felt like dancing, one of her passions. • The surgeon moved quickly, and in short order life would change for the patient.
Gholami felt a connection with him, a Mexican man in his 30s who had come to the hospital surrounded by a very large family. •
“I remember going to the family afterward, saying that we were able to get it all out and seeing the glow in their faces,” she recalls.
“That feeling stuck with me.” • It rekindled a childhood memory: the glow on her own mother’s face when she learned the cancer
had been extracted from her breast. • “I thought, ‘This is what happened to my mom,’ who is now disease-free. This is how she
must have felt.” • And so Gholami, 32, became seduced by the practice of surgery, ultimately setting her sights on a career as a
surgical oncologist. • Now finishing her sixth year as a surgical resident at Stanford Hospital, Gholami, MD, is being raised in
an era of burgeoning surgical technologies, changing training practices and a more collaborative culture that is opening its gates
to women. She must master a breathtaking array of new surgical tools, all designed to minimize the impact of the surgeon’s knife.
With these tools, procedures that once produced a foot-long scar on a patient’s abdomen have been reduced to operations that
By Ruthann Richter
P H O T O G R A P H Y
B Y
M A X
A G U I L E R A - H E L L W E G
Sepideh Gholami is finishing her sixth year
of training to become a surgeon.
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‘ W H E N I WA S A M E D I C A L S T U D E N T,
I REMEMBER A
S E N I O R S U R G E O N S AY I N G , “ B I G H O L E , B I G S U R G E O N . ”
T H A T, O F C O U R S E , H A S C H A N G E D . ’
leave a few pencil-thin marks. And surgeons are pushing the
boundaries with operations that need no incision at all, such as
tumor removal through the nose, the ear or the mouth.
“When I was a medical student, I remember a senior surgeon saying, ‘Big hole, big surgeon,’” recalls Tom Krummel,
MD, the Emile Holman Professor and chair of the Department of Surgery. “That, of course, has changed. We do the
same big operation. We just don’t make a big hole.”
Now surgeons commonly carry out big procedures
through small incisions. They slide in a tiny video camera,
called an endoscope, which transmits the view of the surgical
site to a monitor in the operating room. Through additional
small incisions or through the tube-shaped endoscope itself
they slide in other surgical tools — maneuvering them with
handles that extend outside the body. “The collateral damage
of an incision is no longer the badge of what I can do,” says
Krummel. “It’s harder to work with chopsticks, which is essentially what we’re doing.”
The benefits of surgery’s advances have been enormous
for patients, who now undergo some 50 million surgical procedures a year in the United States alone.
T
H E PRO FE SS IO N GH O LAM I IS E NTER IN G TODAY IS A FAR CRY FRO M TH E S UR GERY OF
when modern practices had
their beginnings, notes surgeon Atul Gawande,
MD, in a 2012 New England Journal of Medicine article. Back then, a Boston surgeon performed the first
reported cataract removal using a cornea knife to successfully
excise the thickened capsule from the eye of an unanesthetized
patient, who regained his sight. Other surgical techniques soon
followed, including extraction of kidney stones and treatment
of arterial aneurysms and gunshot wounds. But these procedures could be brutally painful and were limited in part by the
threat of infection and the lack of anesthesia, whose introduction in the mid-1800s revolutionized the field, says Gawande.
More than 125 years later, the second revolution in surgery came with the advent of endoscopy and other techT H E E ARLY 1800s ,
niques to minimize the intrusion of the surgeon’s knife.
Less-invasive surgeries cause less pain and blood loss, reduce the risk of infection and lead to quicker recoveries, as
many procedures that once required long hospitalizations
can be done without an overnight stay.
A striking example is surgery for patients with an aortic
aneurysm, a bubble in the aorta that can rupture and cause
death. Patients used to undergo a massive, risky procedure in
which surgeons made a foot-long opening in the abdomen to
remove the damaged part of the artery and then sewed a Dacron tube in its place. Now it’s done with two small holes in
the groin, as surgeons snake a catheter up into the aorta and
repair the aneurysm with a stent graft — a procedure pioneered at Stanford. Most patients now go home the next day,
whereas in the past they would typically spend seven days in
the hospital, including two in the intensive care unit.
“The transition to less-invasive, image-guided therapy has
revolutionized vascular surgery and requires us all to continue to learn new skills and innovate, all for improved patient
care,” says Jason Lee, MD, director of endovascular surgery
at Stanford and a principal investigator on several trials of
devices to make it easier for patients to recover from surgery.
With the shift to minimalist procedures, “Surgeons have
had to change mentality,” says David Spain, MD, chief of
trauma and critical care surgery. “If you’re doing a procedure
with small incisions, are you less of a surgeon? It’s kind of
an identity crisis for surgeons,” he says, especially for those
like him who trained in the 1970s and 1980s, when big, open
surgeries were the bread and butter of the practice.
On the other hand, there is the satisfaction of fixing a patient’s life-threatening problem with a few tiny cuts and a quick
hospital stay. “You’re doing the same big surgery on the inside,”
says colorectal surgeon Natalie Kirilcuk, MD, one of a younger
generation of surgeons. “I feel a sense of accomplishment when
I do it with as little external impact as possible. You can take
out an entire colon with a few poke holes and a small incision.”
New imaging and navigation tools also play a key role
in modern surgery, exposing previously hidden structures
in the body to help guide surgeons to minute targets with-
Fiber-optic light casts a red glow as Gholami and David Spain
repair a hernia laparoscopically.
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Gholami thought she’d grow up to be a mechanic. Now she can’t imagine
being anything but a surgeon.
out harming critical structures.
For instance, with advanced brain
imaging, neurosurgeons can visualize structures deep within the skull in
three dimensions, enabling them to
extract malformed vessels through a
5-millimeter (a fifth of an inch) opening or to successfully remove a tumor
near the brain stem, a previously impossible feat, says Gary Steinberg,
MD, PhD, the Bernard and Ronni
Lacroute-William Randolph Hearst
Professor in neurosurgery.
“We couldn’t get there without
devastating the patient,” says Steinberg, chair of the Department of
Neurosurgery. “With current imaging, we can view the brain with a precision of 1 to 2 millimeters,” or less
than a tenth of an inch.
The development of surgical robots, a form of computer-assisted surgery, has added another dimension to the field. With robots,
a surgeon sitting at a console in the operating room can manipulate robotic tools inside the body through a single incision.
Surgeons love working with their hands, and surgical robots are helping bring back the “feel” of traditional surgery
as the surgeon uses dexterous hand and wrist movements to
guide the robotic arms, which serve as a natural extension of
the human hand. “It restores the attributes of open surgery
without making a big hole,” says Krummel, a robotics expert
who came to Stanford in 1998 in part to expand the university’s robotics program by bringing together surgery and engineering. Robots have been used in more than 1.5 million
procedures nationwide and are now the tool of choice in prostate surgery, gynecologic surgery and some other procedures.
With the exponential growth in new tools, even highly experienced hands like those of Jeffrey Norton, MD, the Robert L. and Mary Ellenburg Professor in Surgery and chief
of general surgery, have had to relearn some aspects of the
trade. “You have to learn to do new things. It’s like starting
over,” says Norton, who is widely recognized for his skills as
a surgical oncologist.
At times, Gholami says she has found herself in the operating room with mentors who themselves are acclimating to
some new piece of technology. “They are still in their own
1 0
learning curve,” she says. “So when
you are scrubbing, it may be with an
attending who hasn’t done it many
times. So he or she may be more
cautious.”
As surgical technology has
soared, so has patient demand, along
with the number of skilled practitioners. By 2008, nearly one in every
five active physicians in the United
States was a surgeon, according to
the American College of Surgeons.
These master technicians now have
some 2,500 procedures at their disposal, Gawande notes in his article.
And because of greater ease and
safety, these procedures are performed far more often. At the current rate, projects Gawande, the
average person in the United States will have seven surgical
procedures in his or her lifetime.
“The technological refinement of our abilities to manipulate the human body has been nothing short of miraculous,” Gawande writes.
F
O R G H O L A M I , I T WA S A LO N G , H A R D R OA D
IN TO THE OPER ATIN G R OOM, WHICH WAS FA R
FR OM HER CON SCIOUSN ESS AS A YOUN GST ER
IN HER N ATIVE IR A N . At the age of 5, she fled
the Iranian revolution with her family in the early
1980s and grew up in a hostel for asylum seekers in Germany.
Her father, an auto mechanic, inspired her to use her hands to
fix things. As a child, she remembers repeatedly taking apart
the videocassette recorder to clean and put back together, all
out of sheer delight over the workings of the device. She envisioned herself as a mechanic one day, though it was hardly
a vision of herself as a skilled mechanic of the human torso.
Her life as an immigrant in Germany was hard, so she
jumped at the chance to visit an uncle in Northern California
whom she barely knew. There happened to be some fine universities nearby, and she was fortunate to attend the University
of California-Davis and, later, Stanford medical school, from
which she graduated in 2008.
Even in medical school, surgery was far from her mind.
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She chose it as her first rotation “just to get it out of the way,”
she says.
But she quickly became seduced by the exhilarating tempo
in the OR and the gratification that comes from immediately
fixing a problem and restoring someone to life.
“Surgery is very fast-paced. It is so fast-paced that a lot of
people get lost and think it’s too much for them — you have
to keep 500 things in your head,” she says.
There is a very quick turnaround: “You round on your patients in the morning, then do the operations and in between
cases or after see patients again. It’s not like other fields of
medicine — it’s a very different type of lifestyle. … I don’t
think it’s for everyone, but if you do love it, as I do, you will
feed off it. There may be days when I go without sleep and
am still going. But when I get out of the OR, it doesn’t matter
if I slept last night or not — it is so gratifying. There is nothing else I could envision myself doing.”
The demands are evident on a recent morning, as Gholami works alongside Spain to repair a hernia — a weakness in the abdominal wall that showed up as a large lump
on the patient’s midsection. They take turns controlling a
slim, tubular endoscope, known as a laparoscope, and other tools — periodically alternating places at the operating
table in a quick do-si-do. “See, surgery is like a dance,” says
Gholami, her dark oval eyes framed by her surgical mask
and cap. “Sometimes you have a good partner,” responds
Spain. “Other times you have to lead them around.”
After estimating the size of the surgical site, Spain cuts
out a circular mesh shield — “arts and crafts,” he calls it — to
restrain the gaping hernia. Gholami folds the mesh, inserts
it through the laparoscopic tube and positions it inside the
body. She and Spain then work in tandem over the patient’s
midsection, which glows in the laparoscopic light, their hands
weaving in and out as they stitch down the mesh and staple it
in place. “So pretty,” Gholami says of their handiwork. “Yes,
pretty,” says Spain. “I hope it works.”
Gholami is then off at a run to the emergency room to
examine a young car accident victim, to review scans and order surgery for a man with a perforated bowel, and check lab
results for a gallbladder patient.
“This is the challenge, you see. Everything happens so fast,”
she says as she jogs back to the OR for another hernia fix.
Surgeons are, by nature, nimble practitioners, quick to
move and act. They have to be, for while a patient’s internal organs are exposed, open to possible infection, there’s no
time for long debates about what to do next.
They also feel a special connection to their patients, who
put their full faith in the clinician while anesthetized on the
operating table, often in an undignified pose. “The patients
are completely incapacitated, so when you are in the OR, you
have to do the right thing — make the right decision,” says
Kirilcuk, a clinical instructor of surgery. “I think surgeons
have a lot of passion for their patients because of the trust
that patients put in us.”
G
H O L A M I B E G A N H E R T R A I N I N G AT A T I M E
WHEN THE TEACHIN G OF SUR GERY WAS AT
In 2003, the Accreditation
Council for Graduate Medical Education, the
national accrediting group for medical and
surgical training programs, imposed the first of a new set of
work rules that included a strict, 80-hour work week limit for
residents. These regulations have caused much consternation
among medical educators, particularly in the surgical community. Surgeons in their 50s, like Spain, remember their training days when they virtually lived in the hospital, spending
100 hours a week or more there, on call every other night and
consoling patients at the bedside for long stretches of time.
It was dog-eat-dog in the surgical world those days, with
interns angling to seize every opportunity to be in the operating room so they could beat the competition and survive
the program, he says. With trainees today limited to working 80 hours, “they have 20 percent fewer opportunities to
see stuff,” says Spain, who is the Ned and Carol Spieker Endowed Professor of Surgery. “A lot of people from my generation, who grew up in the competitive era, think those rules
are killing surgery. Though I don’t agree.”
Many argue that surgical trainees back then were so tired
that they were prone to mistakes and weren’t really able to
soak up what they were learning — the rationale behind the
work limits, which were strengthened in 2011. Krummel, the
A CR OSSR OA DS.
‘A LOT O F P E O P L E F R O M M Y
G E N E R AT I O N , W H O G R E W U P I N T H E
COMPETITIVE ERA, THINK THOSE RULES ARE KILLING
S U R G E R Y. T H O U G H I D O N ’ T A G R E E . ’
S T A N F O R D
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department chair, remembers falling asleep at the wheel after
being on call for 36 hours as a resident in Richmond, Va., in
1982. “I could have killed someone,” he says. “I woke up real
fast when I hit the guardrail.” Luckily, no one was injured.
He also questions whether patients benefited from having
tired trainees leaning over the operating table. “We all know
patients for whom we didn’t exactly deliver what was needed,”
he says. “We blundered along. It was learning on the job. We
might have been having trouble getting the appendix out. We
could have used some gray hair in the operating room, but it
was a sign of weakness to call for help. Our trainees today are
much better — they don’t worry about calling for help.”
James Chang, MD, professor and chief of plastic and reconstructive surgery, says when he was a medical student at Yale in
the 1990s, surgery residents routinely slept through lectures.
He saw them as tired, hungry and unhappy. “They couldn’t
see the end of the tunnel in their education.” Today, he says,
“As a result of getting good sleep and having an outside life,
residents are happier people. They’re awake and engaged.”
Stanford has adapted to the new work rules by developing
a more structured curriculum, including time in simulation,
to help residents master the vast body of knowledge and the
bewildering array of technologies and procedures they are
likely to encounter in their practices.
Medical simulation, says Krummel, is crucial. “Simulation
allows you to develop a curriculum in a more thoughtful, organized way,” rather than have residents scrub in for whatever patient happens to come in that day.
He founded the Goodman Simulation Center at Stanford
Hospital & Clinics in 2007 and helped develop the Roy B.
Cohn Bioskills Laboratories, a rare type of facility where surgical trainees use cadavers to hone their skills. Simulation allows
trainees to practice procedures over and over before they even
see a patient, says Lee, an associate professor of surgery. With
simulation, a trainee can face a console resembling a video
game and manipulate wires and catheters inside a box, rehearsing what it’s like to do an angiogram, say, or install a stent.
“We entrust our lives to pilots and they train by working
on simulators,” Lee says. “We entrust our lives to surgeons
and yet we have no metric to measure performance other
than they have practiced alongside someone for five years.
What if pilots didn’t practice until they did the real thing?
“It makes education more efficient, and efficiency breeds
many advantages,” he adds. “They can be here in the hospital
less and incorporate material for a better work-life balance.”
Lee is among those in the surgical community who believe
residents graduate with too little experience to enter independent practice — a subject of much contention. In addition to
1 2
today’s limits on training hours, surgery residents no longer
spend time in the operating room on their own. Changing
government reimbursement practices, which require an attending physician to be present, as well as more scrutiny of
medical procedures by government and regulatory groups,
have limited the autonomy of surgeons-in-training.
As a result, nearly 40 percent of surgery residents said in a
recent survey that they lacked confidence in their skills after
five years of training, according to a study published in September 2013 in the Annals of Surgery. Moreover, 43 percent
of fellowship directors interviewed said incoming residents
couldn’t do 30 minutes of a procedure on their own, though
most said the residents were up to speed by the time they
finished the fellowship program.
Gholami bristles at the idea that today’s surgery residents
aren’t as well-trained because they don’t have enough exposure to different experiences and procedures. “I think that’s
inaccurate,” she says. “Overall you can’t say we’re less trained.
Training today is just different than it was in the past.”
Moreover, she says residents now routinely hone their
skills and gain added expertise in specialty areas by pursuing
one- or two-year fellowships after their four to seven years of
residency, depending on the specialty, and their four years in
medical school. Indeed, more than 80 percent today choose
to go on to fellowship programs after residency, according to
the Annals study.
To help smooth the transition from residency to general
surgery practice, the American College of Surgeons has developed a fellowship. The program supplements the residency curriculum so trainees have the confidence and mastery to
lead independent practices.
N
OT ON LY HAVE SUR GICA L PR ACT I CES A N D
TR A IN IN G CHA N GED, SO HAVE T HE FACES
Where women
were once personae non gratae in the operating room, they are now entering it in record
numbers, accounting for 21.3 percent of the nation’s nearly
136,000 practicing surgeons in 2009. Though women comprise a smaller portion of the surgical workforce than of the
medical profession as a whole — where they account for 30.5
percent — a growing number of female trainees are entering
the pipeline, according to the American College of Surgeons.
Women accounted for 37.5 percent of surgical residents and
fellows in accredited programs in 2008.
Surgery traditionally was considered a demanding job, designed for tough guys, so that even getting married was given
OF SUR GEON S — LITER A LLY.
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‘ S I M U L AT I O N A L LOW S YO U TO D E V E LO P
A CURRICULUM IN A MORE
T H O U G H T F U L , O R G A N I Z E D W AY, ’ R A T H E R T H A N H AV E R E S I D E N T S S C R U B I N
F O R W H A T E V E R P A T I E N T H A P P E N S T O C O M E I N T H A T D AY.
a second thought. Krummel remembers one of his mentors at her husband likes to cook and is willing to console the children in
Johns Hopkins University having to seek permission from his the middle of the night when she is called away to the operating
supervisors to marry. And Spain says in his day, for a surgeon to room to transplant a new kidney or liver.
Maintaining a work-life balance “is definitely a work in
have a wife who was pregnant was considered “marginally acceptable,” as children could prove to be a distraction from work. progress,” she says, though “I have the family life I expected
As department chair, Krummel has made recruiting wom- I would have.”
Gholami says it’s a matter of setting priorities and realizing
en to the department a priority. When he arrived at Stanford
that
at times, “friend and family events will be missed. You just
in 1998, women accounted for only 9 percent of surgery’s
full-time faculty, including those in emergency medicine. have to have a very good support network.” With the new work
Now, 35 percent of the faculty and 45 percent of trainees are hours, she gets a day off a week and occasionally has time for
herself. “I do work out. I do see my friends. It’s not a disastrous
female, he says.
“We’ve been lucky here at Stanford to have female mentors black hole where I disappear for seven years,” she says.
She has a boyfriend, who recently moved to this area to be
who are great role models,” Gholami says. “So the issue of womcloser
to her, and says she sees marriage and family at some
en in surgery is not a problem here, though I’ve heard stories of
point in her future. But she knows it will not be an easy road.
difficulties elsewhere — that there is a gender imbalance.”
“I think if you don’t have a role model, it’s hard for women to “I still think because of the difficulties of having families and
children, it’s going to be tough. I’ve seen mulimagine how they could be surgeons,” Krummel says.
WE B E X T RA
tiple examples of where it’s worked, but it takes
Sherry Wren, MD, a professor of surgery,
Hear an
someone special as a partner who understands.
says she had to almost fight her way into the field
interview with
photographer
... This is probably my biggest challenge, the
more than 25 years ago. “People actively tried to
Max Aguilera-Hellweg
constant struggle of balancing a career in acadiscourage me from going into surgery,” she says.
at http://stan.md/
demic surgery with my personal life.”
“It was the boys’ sport.” But she loved the profes1hPmAaS.
After her residency, Gholami plans to pursion’s artistry and the process of puzzling through
patient problems and making decisions. Her role model was sue a two-year fellowship in surgical oncology, ideally at an
a feisty male surgeon in medical school who urged her to get academic cancer center such as Memorial Sloan Kettering in
New York, where she spent two years during her residency
surgical training.
When she arrived at Yale as a resident in 1986, she was developing a breast cancer therapy. The treatment, a genetione woman among 17 men and had to endure lectures about cally engineered smallpox virus, has done well in preclinical
the style of her curly red hair — which drew more atten- testing, and she hopes to see it enter clinical trials, she says.
At the moment, her patients fuel her passion for surgery,
tion than her performance — and the need to wear pearls in
the operating room, she says. “It was a really different world the ultimate cure for many tumors. She recalls one young
then,” says Wren, associate dean for academic affairs at Stan- man who came in recently with an ailing appendix. He was
fearful of surgery and left the hospital against doctors’ orford’s medical school. “It’s an easier road now.”
Wren helped ease the way for younger surgeons, like ders. He returned that same evening, feeling poorly, and
transplant surgeon Amy Gallo, MD. By the time Gallo be- apologized for leaving. He’d gone home to pray, he’d said,
gan her training at Stanford in 1999, she says gender was less and had hoped his condition would improve. But it had become clear to him that surgery was his best road to recovery.
of an issue in the profession.
“There are certain things where you know surgery is the
Today, Gallo, 38, an assistant professor of surgery, balances
her practice with her life at home with her husband, an account- only way,” Gholami says. “That for me is the ultimate gratiing researcher, and two children — an infant and a toddler. She fication.” SM
eats dinner most evenings with her family and is fortunate that
— Contact Ruthann Richter at [email protected]
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S H E R RY W R E N T H I N K S O F H E R S E L F A S
A S U RG E O N F I R S T.
I N S I D E
J O B :
Surgeons at work
H E R L E F T
H A N D
A SURGEON’S JOURNEY
BACK
As the mental fog from the surgery began to lift, surgeon Sherry Wren asked a friend visiting at her bedside for a dab of lip moisturizer. Her lips were dry, as is common after surgery.
• “I took it with my right hand,” Wren says. “I could move my hand, but I could not find
my face.” Her right hand with the drop of petroleum jelly headed for her chin, completely
missing her lips. Her friend had to help. The two chuckled, assuming that it was the anesthesia, that she was still a bit drugged up. Everything’s fine. Everything’s fine, she thinks.
The spinal cord surgery, a roughly 90-minute procedure on the morning of June 29, 2012,
went well. Except, why can’t my hand find my lips? And my left hand, why can’t I move it yet?
Trac ie White
P H O T O G R A P H Y
S T A N F O R D
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F A L L
2 0 1 2
B Y
M A X
A G U I L E R A - H E L L W E G
1 5
From the Stanford operating room, Wren, 53, profesS U R V I V O R
sor of surgery and associate dean for academic affairs at THREE WEEKS PRIOR TO HER SPINE SURGERY, WREN HAD
the Stanford School of Medicine, had been moved to the AWOKEN AT 3 A.M. IN HER BED AFTER THE 24-HOUR JOURpost-anesthesia care unit. The searing pain of the previ- NEY HOME TO PALO ALTO FROM MALAYSIA AND STARTED
ous three weeks was mercifully gone. The neurosurgeon DIAGNOSING HERSELF. What could cause this crushing chest
had entered through the front of Wren’s neck to fuse two pain that radiates out my back? Aortic dissection? A heart attack?
vertebrae and remove a ruptured disc. Her family and
The shipwreck had occurred during one of her many
friends blamed the disc injury on a high-seas shipwreck deep-sea diving vacations. The 130-foot yacht, the Orienthree weeks earlier, but she wasn’t so sure. Wren had been tal Siren, started taking on water while most passengers and
one of 26 tourists and crew who abandoned a sinking div- crew were asleep in the early hours of June 8, 2012. At 4
ing yacht in rough seas 15 miles off the coast of Layang- a.m., a crew member knocked on cabin doors yelling: “MusLayang Island, Malaysia. All of them survived by navigat- ter with your life jackets!”
ing motorized rafts to shore.
“I never thought I’d hear that,” Wren says. “I knew it was
In the post-anesthesia care unit the morning after her serious.” The boat was taking on water in the rear, but the crew
surgery, Wren next remembered the nurse coming in to didn’t know from where. They were setting up an auxiliary
check her motor functions. About then, the fog lifted, and pump because the main one was damaged and irreparable.
she began to think more clearly. “My left
Two hours later, the power went out on
hand was like a claw. I couldn’t lift my
board, and the crew could no longer steer
left knee. Then my surgeon came to see
the boat as it rocked and rolled through
‘SOMETIMES
me, and I recognized that ‘Oh shit!’ look
15-foot swells. The decision to abandon
STUFF
on his face, because I’ve had that ‘Oh
ship was made at 7 a.m., and all 26 passenJUST HAPPENS
shit!’ look many times.”
gers and crew climbed into the two rafts.
T H AT Y O U
Wren, who has operated on hun“The Thai captain, who couldn’t
CAN’T
dreds of patients herself over nearly
speak English, was curled up in the feP R E D I C T.
three decades, who has prepared so
tal position in the front of one of the
I am the person
many others for the possibility of
life rafts,” Wren says. “He had totally
who really
post-surgical complications, who has
checked out. So it was the dive masters
understands that.
made it ever so clear that no surgery is
and the passengers who had to make
I’m the one
risk free. This time, she’s the one with
the decisions. Some people did start
case in a million
odds in her favor but who still loses
to lose it.” With no response from the
that went
the roll of the dice.
Malaysian navy to the crew’s mayday
wrong.’
It was the correct diagnosis. The corradio calls, the survivors decided to
rect treatment. There was no surgical
make their own way to the bits of land
error. And yet somehow, the veteran surgeon who makes a visible between ocean swells. All 26 made it. All survived.
living with her hands woke up partially paralyzed. The unex“Shipwreck almost over!!!” Wren posted on Facebook
pected complications included paralysis of her left hand and once she made it to shore. “Still can’t believe all my gear and
her left leg, and a weakened right hand. Already she thinks, stuff is 6,000 ft. below the ocean.”
Will I still be able to operate? Already she thinks, What am I if
The survivors spent the night in the lone hotel on the isI’m not a surgeon?
land then hopscotched across Asia to get home. Wren’s trip
“Look, something can always go wrong. I’m the poster involved five connecting flights, with a particularly long laychild for that,” she says, telling the story almost two years over in the Narita airport in Japan.
later, sitting at her desk in her office at the Veterans Affairs Palo Alto Health Care System. “I see a lot of paE XC R U C I AT I N G
tients. I tell them what the ‘percentage of chance’ is for a SHE’S STILL NOT SURE WHAT CAUSED THE HORRIBLE
certain complication, but that’s pretty much meaningless. PAIN. MAYBE IT WAS THE STRENUOUS TWO HOURS SPENT
Sometimes stuff just happens that you can’t predict. I am IN THE RESCUE CRAFT. Wren stepped in to help refill the
the person who really understands that. I’m the one case outboard engine’s tank, lifting heavy gas cans as the craft
in a million that went wrong.”
crashed through those 15-foot swells. Or maybe it was the
1 6
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CLO S I NG T I M E
Wren sutures an incision in a patient’s abdomen at the end
C OofN aT surgery
I N U E to
S remove and
O Nexamine his
P Agallbladder.
G E
X X
S URE , S T RONG HAN D S
Wren and general surgery resident Arghavan Salles, MD, PhD, cut, retract, grasp, clamp, cauterize, suction and suture.
six-hour layover in Narita where she slept upright in a chair,
her head drooping. Or maybe it was just an accumulation of
damage from the many years she has spent standing up on a
stool in the operating room so that her 5-foot, 3-inch frame
could bend over and she could tilt her head down to see inside her patients’ abdomens as she cut and sutured and toiled
to save their lives.
Whatever the cause, the pain that ripped through her
chest was so excruciating she was forced to wake her husband. He wanted to rush her to the emergency room right
away, but she held out until 7 a.m. — advice she would never
give anyone else. “No one wants to be seen naked in front of
their friends at work,” she says.
At the Stanford ER, the potential diagnoses came and
went until finally someone suggested nerve damage and the
neurologist arrived to examine her. There were more tests,
more speculations, then somewhat randomly, the medical
staff started flicking the middle finger on each of her hands.
“I’m thinking ‘What the heck?’” she says. She had tested
positive for the Hoffman’s reflex test, apparently rarely seen.
When the middle finger is flicked and the last joint of the thumb
1 8
flexes at the same time, this indicates problems in the nerve
system of the spine. The diagnosis: acute spinal cord compression. A spinal disc herniation was bulging onto the spinal cord,
flattening it like a ribbon. The solution: surgical removal of the
bulging disc and fusion of vertebrae 5 and 6, and 6 and 7.
For the next three weeks while waiting for surgery, she
slept sitting up to control the pain. When the day of surgery
finally arrived, the pain was so unbearable that the surgical
team had to knock her out with medication before she could
be laid flat on the operating table. Perhaps that’s when the
complications occurred — the damaged disc bulging just the
right way, putting pressure on the nerves just the wrong way.
A
S U R G E O N ’ S
L I F E
IF SURGEONS HAVE A STEREOTYPE, WHICH THEY DO OF
COURSE, WREN FITS MUCH OF THE BILL: TOUGH, FEAR-
Her specialty as a
professor of surgery at the Palo Alto VA is high-risk gastrointestinal cancer surgeries — like taking out a 25-pound liver
tumor or removing a tumor from the pancreas with the notoriously difficult Whipple procedure. That’s what she lives
LESS, STRONG, IMPATIENT, EFFICIENT.
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to do. Like most surgeons, she has always been commanderin-chief in the operating room. It is her stage. She jokes. She
picks the music. She hums along. She gives the orders and
then taps her fingers with irritation on the sides of the operating table until they are followed. The OR is her universe,
her world. Self-confidence is key in this life-or-death arena,
where slipshod work is not an option. Once a body is sliced
open, time is precious. Speed is essential. The sooner the patient gets sewn back up, the better. Surgery is always a risk.
Minimizing that risk and achieving results is her job.
It’s more than her job, of course. It’s her calling.
“The first time I saw surgery, I thought, ‘Oh my God!
That’s what I want to do. You get to fix it!’” says Wren.
It wasn’t her lifelong dream to become a surgeon. Wren
was just a good student who grew up in Chicago, where her
father had a TV repair and car radio installation shop, and
her mom stayed at home to raise Wren and her three brothers. She was the first and only person in her family to graduate from college, studying biology at Carleton College, in
Minnesota, then attending medical school at Loyola University in Chicago. That was where she first saw surgery and
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fell in love. Once she became a surgeon, “I’ve always defined
myself first as a surgeon,” she says.
Wren is married with no children. Her two bull terrier
dogs have personalities to match her own — stubborn, independent, lovable. Almost equal to her passion for surgery
is that for deep-sea diving that has taken her to the wilds of
New Guinea, where she danced in the rain with the natives,
ate foot-long tree worms and survived a cyclone at sea.
“Sherry will try anything,” says her friend and diving partner Lynne Maxwell, MD, an anesthesiologist from Philadelphia who saw firsthand the eating of the worm and was with
her during the Malaysian shipwreck.
That same fearlessness is present in the OR.
Wren likes the challenge of performing high-risk surgery.
She takes on the “peek and shriek” cases: “Another surgeon
will open up a patient and say, ‘Ohmigod, it’s too this or too
that,’ and close him back up,” Wren says. Not Wren.
“She’s just a powerhouse,” her friend and fellow surgeon
Myriam Curet, MD, says. “She takes care of very sick patients with very difficult problems. Everybody trusts her.”
The scuba diving gives her a release from this stress-
1 9
ful world of high-risk surgery, she
like a well-known neighborhood map.
says, although others say that she’s
Her students, the young doctors and
‘
I
C
A
N
F
E
E
L
just an adrenaline junkie — a stereosurgeons gathered around the patient’s
typical surgeon.
chest, watch her hands closely. They
HIS
“I do operations where I really can kill
study those hands. The hands teach them
PULSE
somebody,” she says. “I’m always worrytheir anatomy lessons so that someday
BEHIND
ing about whether the patient will be OK.
they too can save lives. So that they too
HIS
It’s critical to unwind. Diving is the only
someday can perform the Whipple, the
B I L E D U C T,
time I can shut that out.” Which she does
crown jewel of surgeries.
WHICH MAKES
on a boat out in the middle of nowhere
“That’s why I keep telling you you’ve
ME...,’
with no cell reception, no Internet sergot to know your anatomy,” Wren says,
her voice trails off.
vice. Just the deep blue sea and swimming
as she constantly quizzes them on the
The room tenses.
with the fish four to six hours a day.
names of organs and veins.
‘That makes me want
In her spare time, Wren volunteers for
Like a ballplayer, it’s said that she
to get down to
Doctors Without Borders, performing
has “good hands,” that she has amazing
business.’
medical missions to Chad, the Congo,
hand-eye coordination.
Ivory Coast. She has saved many lives
“Don’t dig into the liver,” she warns
with the power and skill of her hands — popping dislocated the chief resident as she guides his hands through the labyhip joints back into place, relieving brain bleeds with a hand rinth of intestinal organs. The liver, a large, dark mass, rests
drill, doing C-sections.
a bit ominously just above the intestines.
“You have no idea how physically hard it is to crank a 6-mil“I can feel his pulse behind his bile duct, which makes
limeter pin into someone’s femur with a hand drill,” Wren says. me...,” her voice trails off. The room tenses. “That makes me
“And I’m strong.
want to get down to business.”
“I could survive with my legs paralyzed, but not my hands.”
The minutes tick past as the surgeon and chief resident cut
She takes enormous pride in her powerful hands. They are and sew, cut and sew. Back and forth they pass the scissors and
blessed hands, no question. So when, suddenly, those hands the needles and the suctioning instruments.
lost their strength, when the left hand began to shrivel before
The wall clock moves past 10:30 a.m., past 11:30 a.m.
her eyes and started to look skeletal, it shook her to the core.
Her left hand works as hard as the right. It’s the support
These aren’t my hands. They’re an alien’s hands, she thinks. hand. The stalwart, dependable, indispensible force. The left
They don’t belong to me.
hand digs down deep into the guts.
“All right, let’s get this gallbladder out,” she says. The surgery had really only just begun.
G O I N G I N
THEY ARE SMALL, FEMININE HANDS. THE FINGERS ARE
SLENDER. THE WHITE, UNMANICURED NAILS ARE VIS-
R E H A B
IBLE THROUGH CLEAR, SURGICAL GLOVES. HER VOICE IS
FOR ABOUT A MONTH AFTER HER SURGERY, WREN HAD
LOUD. HER PERSONALITY FILLS THE ENCLOSED, WHITE-
TO USE A WALKER. SHE NEEDED HELP TO WASH HER HAIR.
Her hair is naturally curly and
red. She’s a bit like a small tank, one that can bulldoze its way
through walls. Not much can stop her.
It’s 9:30 a.m. The abdomen incision is made. Six scrubswearing, plastic-gloved medical professionals surround an operating table at the Palo Alto VA hospital. The workday begins.
Wren’s hands slip nicely into the open, bloody abdomen.
They work in sync with each other, and gently push around
the internal organs, the small and large intestine, folding
back the peritoneum — the lining of the abdominal cavity —
searching and uncovering the vena cava, the gallbladder and
the pancreas. She reads the internal anatomy of her patient
SHE COULDN’T DRIVE. SHE WAS FORCED INTO DEPEN-
WALLED OPERATING ROOM.
2 0
She started seeing a psychiatrist
to help adjust. Still, the day after she returned home from
neck surgery, she was back at work. Friends told her to go
back home to finish recovery, but she returned again the next
day. She could still perform many of her duties, treating patients at the clinic and continuing her teaching rounds.
But the doors to the OR were closed.
“It’s not easy to slow her down,” says her friend Kim
Rhoads, MD an assistant professor of surgery at Stanford. “It
takes a lightning strike from the universe, something like a
shipwreck. Seriously, it took that whole ship sinking.”
DENCY, AND SHE HATED IT.
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S T A N F O R D
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Nerve recovery can continue for up to two years after dam- developing a reputation as an expert in another area.”
After six months of hand rehab, Wren finally walked
age. But it happens slowly, nerves growing about 1 millimeter
through
the operating room doors once again dressed in
per day. Without the nerve innervation the muscles will atrophy. Exactly how much the damaged nerve will grow back in scrubs. She started with the short, 45-minute, easy-to-do
Wren’s case remains an unknown. Some of her motor func- surgeries — the hernias, the gallbladders. Her technical skills
tions came back quickly. Soon enough, she could walk, drive a were still good, she could see that. The surgeries went well.
car and wash her own hair. The right hand regained much of its But still, there was something wrong.
“I went back in very slowly. Everyone said, ‘You’re doing
strength as well. But the left hand, the one frozen in the shape
fine.’
But I made my partners watch me to make sure I was
of a claw immediately after surgery, remained a problem.
In the first few months after surgery, Wren’s No. 1 motiva- doing everything right. I would go into the scrub sink and
tion was not just getting back to operating, but to return to those look at my hands and think, ‘These are not my hands.’
“For the first time in my life, I felt I’d lost all confidence. I
marathon surgeries. The ones that last eight, 10, 14 hours. Even
felt
horrible. I could see objectively that I was operating fine.
though she’s right-handed, she needs a strong left hand as well to
But I couldn’t get it out of my mind that I was doing something
do those surgeries. She wanted the Whipple back.
“My left hand is the control hand that sets everything dangerous.” The depression descended over her like a blanket,
blinding her. She didn’t want to get out of bed in the morning.
up,” she says. “There are no one-handed surgeons.”
“Like many people, I saw it as a personal
But as the months passed, her left
weakness that I could not dig myself out of.
hand began to atrophy. At some point
I was in such a dark place. I thought, ‘My
during those months of rehabilitation —
‘ I F E LT
hand is horrible. I’m a horrible person.’”
even though she knew objectively that it
HORRIBLE.
On a sunny Sunday morning in the
made no sense — her hands started to
I COULD SEE
winter of 2012, Wren sat in the backyard
look foreign to her. My hands are stronger
O B J E C T I V E LY
of her friend Curet, the fellow surgeon
than these. These are someone else’s hands.
T H AT
and consulting Stanford professor. While
“It was so depressing,” Wren says.
I WA S
they watched Curet’s 6-year-old twins
“My entire life I’ve always had really
O
P
E
R
AT
I
N
G
jump on a trampoline, Wren opened up
good hand-eye skills. I was really strong
FINE.
about the depression.
for a woman. I regained my dexterity
But
I
couldn’t
get
“I remember being really surprised
quickly after surgery, but the nerves were
it out of my
how deeply this had affected her,” Curet
not innervating my muscles. My muscle
mind that I was doing
says. “What all of us saw at work was
strength would die in like a second.”
something
that she was back to doing cases. She
For the next six months, she did six to
dangerous.’
had this external confidence. Everything
eight hours of occupational and physical
looked fine.
therapy each week. Her competitive na“She seemed too depressed to be able to focus. I told her
ture kicked in, and she tended to overdo it. Her home filled
with rehab equipment — weights, exercise bands, exercise about my own experience with this. I told her it seemed to
balls. She pushed hard. Sometimes she met Rhoads for lunch me like her depression might do well with medication, mayon Fridays and talked about her goals. What would she do be antidepressants.”
Within a week and a half after taking an antidepressant,
if she didn’t get enough hand strength back to be able to do
Wren says she began to feel better. She took the medication
the Whipple?
“We’d talk about, ‘Do you have to keep doing Whipples?’” for six months, saw the psychiatrist for a year. Today, her left
Rhoads says. “There’s a kind of pecking order of operations, accord- hand is still weaker than it was, but that’s OK. The depresing to their risk. The Whipple is the Cadillac of operations and at- sion is gone.
“It makes no sense to me why the medication worked, but
tests to a surgeon’s technical skills. It’s the tippity-top of the pecking
within a week and a half, I began to feel better,”
order of operations. It’s very high-risk surgery.
WE B E X T RA
Wren says. “It allowed me to have confidence
“She was trying to figure out who would
Hear a conversation
with surgeon
again. I stopped looking at my hands as if they
she be without this part of herself. I think that’s
Sherry Wren at
were an alien’s. Myriam telling me about her
when she started teaching others her global
http://stan.md/1ipsp9C
health skills, holding classes for other surgeons,
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S T A N F O R D
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Surgeons at work
M E DICAL
A C O N V E R S AT I O N
W I T H C N N ’s
S A N J AY G U P TA , M D
He’s a practicing
neurosurgeon
and chief medical
correspondent for CNN.
But right now,
Sanjay Gupta, MD, is making
news for “doubling down”
on his support for
medical marijuana and
apologizing “for having
not dug deeply into
the beneficial effects of
this plant, and for writing
articles dismissing
its potential.”
Illustration by TINA BE RNING
C OVE RAG E
Gupta joined CNN in the summer of 2001. Since that time he’s
covered floods and earthquakes, tsunamis and oil spills along with
the wars in Iraq and Afghanistan. He’s also an assistant professor of
neurosurgery at Emory University School of Medicine and associate chief of the neurosurgery service at Grady Memorial Hospital in
Atlanta. So where, you wonder, does he find time to write a novel,
Monday Mornings, about life in the ER? Responding by email from
Guinea where he was reporting on the Ebola outbreak, Gupta said
that it took him 10 years on and off to write the novel. “I write a lot
on weekends, at night and on planes. Many of the characters were
amalgamations of people — real and fiction. Once I understood
my characters (which took the longest time), the stories came more
quickly.” Paul Costello, executive editor of Stanford Medicine, spoke
with Gupta about surgery, medical reporting and his efforts to combat loneliness in America.
PAU L CO S TELLO: In 2009, you wrote an article in Time opposing efforts to legalize the medical use of marijuana. You’ve changed your
position. Why?
SANJAY GU P TA: Typically as a reporter, I survey the medical literature
on various topics, everything from heart disease, diabetes, neurodegenerative disorders, but also things like medical marijuana, potential new treatments for all sorts of things. When I looked at the
literature [about marijuana] coming out of the United States, I just
wasn’t that impressed. But I started to become aware of literature
from smaller labs outside of the U.S. I also realized that many of the
studies that were being done in the U.S. were designed to find harm.
spending my time on pediatric rotations. I did a rotation in neurosurgery and it was one of those things where I immediately fell in love.
If someone has a problem in their brain or their spinal cord, you’re
going to address it that day. It feels very concrete. I found the ability
to take care of patients more immediately to be very gratifying.
What makes a great surgeon?
One of the misconceptions is that these people are physical geniuses — extremely talented with their hands. There’s a small
percentage of people who can’t do it, the coordination and dexterity
just isn’t there. But I think the vast majority of people can be trained.
You have to be somebody who works well under pressure but is
also not afraid to ask for help. That’s key. What you find among the
very best surgeons: Their judgment is impeccable. They know not
only where to operate but what operation to do. If they’re in a situation that is challenging or they don’t feel like they have complete
control, they can ask for help.
COS TE LLO:
G UP TA :
COS TE LLO: Have you thought about how surgical training could be
improved?
G UP TA : When patients come to my office, fewer than half of them
really need an operation. They’re coming to be evaluated. But what
they are really coming for is knowledge — sometimes the most important knowledge that they’re going to hear for a long time, as it directly affects their lives. So it’s really important to make sure we train
people to dispense that knowledge in a careful, compassionate way.
You recently launched a campaign to combat loneliness.
How did this come about?
G UP TA : The campaign, Just Say Hello [http://www.oprah.com/
health/Just-Say-Hello-Fight-Loneliness], emanated from a lot of
conversations I had with professionals in the field of psychology and
psychiatry after the multiple mass shootings over the past couple of
years. As a medical reporter I find myself reporting on a lot of these
COS TE LLO:
Do you worry at all about the long-term risks of marijuana on cognitive and psychiatric disorders?
G UP TA: Yes, I do. Yet the literature is pretty compelling with regard
to the treatment for specific diseases, such as epilepsy, neuropathic
pain and muscle spasms brought on by M.S. This is in addition to the
things most physicians think marijuana may have a use for: curbing
COS T ELLO :
‘ D E S P I T E A LL T HINGS T HAT WOULD
suggest otherwise — social media and seeming to be more interconnected than
ever before — we may have become more lonely as a society.’
the side effects from chemotherapy, stimulating appetite.
Right now it’s a schedule-1 drug, ordained to have no medicinal benefit. It’s very hard to do double-blinded, randomized, prospective trials on something that is already preordained to have no
medicinal benefit. No one is suggesting there aren’t any potential
downsides to this as a medication. But in order to get answers to
some of these questions and obtain the more satisfactory evidence
in the United States, you have to make it easier to study.
Why a career as a neurosurgeon?
A lot of my colleagues wanted to be brain surgeons since
they were kids. That wasn’t the case for me. I thought I was going
into pediatrics when I started medical school. I loved kids and loved
COS T ELLO :
G UP TA:
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things. People always ask the same question, of why this happened.
There’s never a satisfactory answer.
But I spent a lot of time with specialists just trying to understand
what they thought of these shootings. Often someone is described
as a loner or as lonely or isolated. That came up many, many times.
Despite all things that would suggest otherwise — social media and
seeming to be more interconnected than ever before — we may
have become more lonely as a society. The consequences of feeling
lonely, feeling that you live on the fringe, that’s what really fascinated
me. When I talked with scientists who study loneliness, they told me
a person relegated to the fringe would perceive things that seemed
innocuous to most people as a threat.
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Surgeons at work
I N C R E D I B L E
F O C U S I N G
I N
T H E
E F F O R T
C A R T I L A G E
O N
T O
G R I S T L E
I M P R O V E
J O I N T
R E P L A C E M E N T S
C
ONSTANCE CHU WAS A MEDICAL STUDENT
OBSERVING A SURGERY PERFORMED BY HER TEACHER WHEN SHE CAUGHT HER FIRST GLIMPSE OF HUMAN ARTICULAR CARTILAGE, THE SMOOTH, GLISTENING COATING THAT COVERS THE ENDS OF BONES AS
THEY MEET AT THE ANKLE, KNEE AND HIP. • “YOU ONLY HAVE ONE CHANCE AT THIS,” HER TEACHER, HENRY
MANKIN, MD, CHIEF OF ORTHOPAEDIC SURGERY AT MASSACHUSETTS GENERAL HOSPITAL, TOLD HER. “IF
YOU DAMAGE THIS CARTILAGE, IT DOESN’T GROW BACK.” • This was the early ’90s, and Mankin was considered one
of the 20th century’s leaders in research on cartilage — especially articular cartilage, which is thought to be incapable of recovery
from injury because it lacks nerves and blood, the body’s two most important tools for healing. Its basic metabolism was believed
to be so slow that the tissue was considered nearly inert. With that set of characteristics, the only hope for damaged joints was to
replace them with something artificial. • Although she started her career replacing joints with artificial materials, Chu is now a
Stanford professor of orthopaedic surgery, treating the kind of cartilage and ligament injuries that typically lead to joint replacement. She is convinced, however, that articular cartilage can heal itself. She and several Stanford colleagues are researching ways
to predict and track the damage to this all-important bone protector, to find new approaches to its repair and to stem the rapidly
rising flood of people whose joints are wearing out. • “The next generation of orthopedic devices,” says William Maloney, MD,
professor and chair of orthopaedics at Stanford, “is going to be biologic in nature: protein and cells, not metal and plastic.”
By Sara Wykes
I L L U S T R A T I O N
S T A N F O R D
M E D I C I N E
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Cartilage research has only recently gained wider interest.
In fact, when she was a young researcher looking for ways to
grow cartilage from stem cells and to capture images of articular cartilage behavior, Chu says, “people were acting like I was
crazy. Now everybody wants to be able to do it.”
Understanding articular cartilage is at the heart of that next
generation of orthopaedic devices, pushed by a rapidly rising
need for joint replacement. Many people — 27 million of them
in the United States — are familiar with the pain caused by
damaged articular cartilage, otherwise known as osteoarthritis.
That condition is the primary impetus for the knee and hip
replacements already given to more than 7 million Americans.
Osteoarthritis is distinctly age-related, so the aging of the 49to 68-year-old baby boomers — now about 15 percent of the
population and estimated to rise to nearly 20 percent by 2030
— will push even higher the numbers for osteoarthritis and the
joint replacements that usually follow.
Just last year, another 800,000 knees and hips were replaced.
Joint replacement numbers are rising so fast that the American
Academy of Orthopedic Surgeons projects that by 2030 the
combined demand for hip and knee replacements may outstrip
the availability of surgeons to perform the procedures.
The current plastic and metal replacement parts are good
but not perfect, and don’t function as well as a normal joint.
Ultimately many of the implants must themselves be replaced. The metal alloys in implants can corrode; plastics,
too, will wear out. And metal particles shed by some implants
can destroy healthy tissue or cause poisoning.
Cost is also a driver. In 2005, orthopaedic-implant costs
in the United States were $5 billion, double what they had
been in 2002. Now, nearly half of Medicare’s annual $20 billion tally for implanted medical device coverage is spent on
orthopaedics. Effective prevention or earlier biologic treatment might reduce the rate of replacements and the subsequent cost of those surgeries.
Orthopaedists are now aiming their work at the key puzzle
of how bones and articular cartilage behave. Articular cartilage is perhaps the most challenging component of developing new biologic devices for joints. Most of us might look to
our bones as the workhorse of our skeleton, but it is articular
cartilage that, ounce for ounce, does the most with the least.
Generally no thicker than a dime, it helps our joints remain
strong against forces that with each step can add up to three
times our body weight.
No small job, that. The average adult takes 1.2 million
steps annually. Stair climbing triples the load joints bear.
Mankin and two co-authors of a 2005 lecture on articular
cartilage called it the biggest contributor to the “extraordi-
2 6
nary functional capacities” of the joints it protects, allowing
those joints to move with a level of friction less than any artificial substitute, putting to scorn all machinery, including the
metal joint replacements then available.
T
HE FIVE ZONES OF AR-
TICULAR
CARTILAGE’S
INTERNAL
ARCHITECTURE
ARE A MARVEL OF FUNCTIONAL DESIGN — A SERIES
OF DISTINCTIVELY DIFFERENT CELLULAR ARRANGEMENTS THAT CONTROL AND DIRECT WATER, THE
of articular cartilage. That water acts as
the primary weight-bearing element in the cartilage. The cartilage’s layers — some horizontal, some vertical and some in random array — work with the cells’ biochemical reactions to manipulate water within cartilage. “Mother Nature did a brilliant
job of engineering,” says Jason Dragoo, MD, associate professor
of orthopaedic surgery at Stanford, “to the point that it is difficult
to re-create. This is one of the body’s most complex tissues.”
If researchers succeed in re-creating articular cartilage,
it won’t be the first time that a natural substance has been
chosen to replace a damaged joint. The first experiments in
joint replacement began in the late 19th century with a German physician who used ivory to replace a young woman’s
knee. He had already tried aluminum, wood, glass and nickel-plated steel. In the 1930s, an American doctor tested a
tempered glass called Pyrex before finding a chrome-cobalt
alloy to be more stable.
The surgery has evolved since the first total knee replacement
in 1968. Surgeons make a long incision from about 2 inches
above the knee to about 2 inches below. The surgeon cleans and
prepares the ends of the thighbone and the top of the shinbone
to accommodate the replacement parts. The thighbone is capped
with a metal covering that mimics its old, rounded end. Into the
top of the shinbone, surgeons insert a stem that will support a circular, plate-shaped metal covering. On top of that covering rests
a similarly shaped layer of plastic whose upper surface is curved
inward to accept the rounded end of the thighbone. The back
of the kneecap is fitted with a metal or ceramic button. With
those components in place, the thighbone is rotated around on
the shinbone’s tray, with the patella in place to cover the joint.
The great hope is that insight into the biology of cartilage
will allow damaged cartilage to revive, making such drastic
intervention unnecessary.
Clinical trials are taking place around the world to test
implants made of materials designed to stimulate new bone
and cartilage formation. Many of these materials, however,
MAIN COMPONENT
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are created from cadaver tissue, which isn’t easy to come by.
Treatments that rely on the patient’s own cells to make replacement cartilage are also plentiful, though not very successful so far, Maloney says. It will take another decade before cell-based cartilage repair will protect joints well enough
for any activity that stresses our knees and hips beyond basic
movement, he says.
Later this year, Dragoo plans to start testing a knee joint repair
treatment that uses stem cells from the fat pad under the kneecap
as a repair material. He will harvest those cells using minimally invasive instruments, put them in a centrifuge to concentrate them,
add biologic glue made from blood, and insert that mix into the
cartilage defect. “We think the fat pad is there for a reason,” Dragoo says. “We’re taking an immature cell and supplying it with the
right environment in the hopes that it stays a cartilage cell.”
‘ M O T H E R
N AT U R E
O N E
O F
D I D
T H E
A
B R I L L I A N T
B O DY ’ S
M O S T
Even more reliable, Dragoo says, will be the ability to instruct
a 3-D printer to re-create articular cartilage. That may be possible in a couple of years on a small scale to test as a repair for
the pothole version of cartilage defects. “And when we can treat
potholes,” Dragoo says, “then we can resurface the whole street.”
O
THER STANFORD RE-
SEARCHERS ARE FOCUSED NOT ONLY ON BETTER
UNDERSTANDING
HOW
TO
WORK
WITH
TRANS-
PLANTED FORMS OF CARTILAGE REPLACEMENTS, but
also on how to prevent and predict cartilage damage. Marc
Safran, MD, professor of orthopaedic surgery, has years of
experience treating athletes’ cartilage injuries. He and Garry
Gold, MD, a professor of radiology, are studying the knees
of marathon runners using imaging to capture what the
stress of running does to cartilage, and to investigate ways
to prevent such damage. Safran has also been identifying the
anatomic differences that make someone more vulnerable to
joint damage. “If we can prevent this damage from happening, that will be the real key.”
That kind of research is valuable because articular cartilage can
be damaged by more than just the aging process. If the contact
points of the knee joint are altered, then the cartilage’s protective
barrier no longer makes contact properly. And the most often
damaged element of that arrangement is the anterior cruciate
ligament, known more colloquially as the ACL. Young athletes
who tear their ACLs set in motion a deterioration of cartilage
S T A N F O R D
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that can lead to early osteoarthritis and early joint replacement.
Cartilage and the discs between vertebrae in the spine have
many similarities. Another professor of orthopaedic surgery,
Serena Hu, MD, has focused on the discs of the spine, searching for new ways to preserve disc strength and function. “By the
time a patient comes in with a worn-out disc,” Hu says, “it’s too
late to repair or regenerate it. We want to be able to predict if
someone with early degenerated, non-painful discs is likely to
develop more-degenerated, painful discs. Understanding more
about the genetics of disc degeneration will help us determine
who will benefit from early intervention.” She has also seen in
her research that movement of the spine reduces deterioration.
“I’ve always believed that you should stay active,” she says.
When Chu started her career, she was one of only a few researchers working on articular cartilage, but now she has plenty
2 0 1 4
JO B
O F
E NG I N E E R I NG .
C O M P L E X
T H I S
I S
T I S S U E S .’
of collaborators. In fact, the International Cartilage Repair Society, formed in 1997, now has more than 1,300 members in
64 countries. At Stanford, Chu and Tom Andriacchi, PhD, a
professor of mechanical engineering and of orthopaedic surgery, are studying how abnormal movement patterns damage
articular cartilage. She is working with radiologist Gold on the
next generation of MRI techniques to detect cartilage behavior.
And she is collaborating with Bill Robinson, MD, PhD, an associate professor of medicine, to develop a blood test “to give
us an idea of what is going on with articular cartilage without
having to do imaging,” she says.
But her longest-running project, funded since 2006 by the
National Institutes of Health, seeks a way to diagnose osteoarthritis noninvasively before joints start hurting. The key is
to recognize damage inside cartilage before the tissue is beyond repair. The current method for diagnosis, arthroscopy,
is a surgical procedure in which a camera is inserted inside
the joint. She has been looking for a noninvasive alternative.
So Chu is thrilled by the results of one of her recent experiments, published this summer. The study examined the ability of
a new imaging technique called ultrashort echo time MRI mapping to assess cartilage health. It was a small study of 42 subjects:
31 with ACL tears and 11 uninjured. It showed that the MRI
method was able to detect damage, and something far more exciting, something that her mentor told her more than 20 years
ago was impossible — that articular cartilage could recover. It
took time, but after a new type of ACL reconstruction and a year
of rest, most of the subjects’ injured cartilage did heal. SM
— Contact Sara Wykes at [email protected]
2 7
I N S I D E
J O B :
Surgeons at work
SCULPTING
BONES
A T E C H N I Q U E T H AT R E Q U I R E S
PRECISION, ARTISTRY AND, FROM
T H E PAT I E N T, T R U E G R I T
I N A L IT T L E R E D H E LLO K ITTY BAG, 7-YEAR- O LD GIA N A B R OWN KEPT HER SUR GICA L A DJUSTMEN T TOOLS: T WO SMA L L
W R E N C H E S , SIX CO LO RE D P E NC ILS AND A P RIN TED A DJUSTMEN T PR ESCR IPTION SHEET. TWO OR THR EE TI MES EACH
DAY FO R M O R E T H AN S IX M O NTH S , S H E SAT D OWN , TOOK OUT HER TOOLS A N D CHECKED WHICH SETTIN GS SHE N EEDE D TO C H A N G E O N TH E BRAC E AFFIXE D TO H E R LOWER LEFT LEG. The brace, known as an external fixator, formed a cage
around her limb, with six color-coded, extendable metal bars, called struts, connecting two flat, metal rings — one encircling
her leg just below her knee, the other near her ankle. The rings were fastened to her leg by long, thin pins that went into her
tibia — the larger of the two long bones in the lower leg. Giana, with temporary flower tattoos encircling her wrists, used
one of her wrenches to turn adjustment knobs on the struts to the prescribed numeric setting, checking each one off with a
matching colored pencil. • When Giana turned the knob, it lengthened the fixator, thereby widening a surgically created
gap in her bone. In that gap, bone-producing cells called osteoblasts were collecting across a bridge of collagen that the bone
itself had created in the first days after surgery. Stretching this gap gradually, exactly 1 millimeter a day, fostered the process
of cellular generation, called “distraction osteogenesis,” which ultimately increased the length of her tibia bone by nearly 3
inches. • Though it’s not a stretch to say an external fixator resembles a medieval torture device, orthopaedists and patients
By Julie G reic ius
P H O T O G R A P H
B Y
M A X
A G U I L E R A - H E L L W E G
G IANA BROWN’S LEFT LEG WAS LENGTHENED BY 3 INCHES
TO MATCH HER RIG H T.
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alike see it as a modern technological wonder. The apparatus
on Giana’s leg, called a Taylor Spatial Frame, makes possible
highly precise, computer-guided bone lengthening and repair. But it’s not for the faint of heart.
“Sometimes it would take us 15 minutes to get to the
number we needed,” says her dad, Greg Brown. Giana was
particularly sensitive to even the slightest pain, but like all
patients using the brace it was up to her or her caregivers to
make the daily adjustments. “She’d move it a little, feel it and
stop for a moment. But she was in control.”
S
U K I AND GREG BROWN FIRST NOTICED A N
IN C REAS ING U NE VENNESS IN TH EIR DAUGHT E R ’S LE GS W H E N S H E WAS AB OUT TWO
“The first sign was when she was
running,” says Greg. “Her left foot looked
like it was pointing out way off to the left, more than
45 degrees, and her left leg wasn’t as long as the other.”
Her parents began by putting inserts in her shoes, and
eventually had lifts — platforms that would equalize her leg
length — added to the soles of her shoes. “We realized that
her hips weren’t lining up,” says Greg. “It was getting worse.”
Shortly after Giana’s fifth birthday, her primary care doctor referred her to Lawrence Rinsky, MD, chief of pediatric
orthopaedic surgery at Lucile Packard Children’s Hospital
Stanford and professor of orthopaedic surgery at Stanford’s
School of Medicine. The X-rays Rinsky ordered for Giana
showed benign tumors inside her bones, mostly at the ends
of her long bones — the femur (in the thigh) and tibia (in the
shin). He also found some in the middle of her femur. Rinsky
diagnosed her with “non-ossifying fibromas,” a disorder that
would make her bones vulnerable to fracture.
A N D A H ALF.
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Just a few months later, in October 2011, it became clear
that Giana’s bone disorder was more rare and complex than
anyone had suspected. At her school’s after-care program,
she slipped on a book and fell, and in the next moment she
was curled in a ball on the floor. “She wasn’t screaming or
crying. She just wouldn’t budge,” says Greg. “It was frightening because I couldn’t help her. So we called an ambulance.”
At the hospital, Rinsky was out of town, so orthopaedic
surgeon Jeffrey Young, MD, took the case. X-rays revealed
a spiral fracture that twisted smoothly down Giana’s femur,
splitting it clear through. “We couldn’t believe it,” says Greg,
who quickly learned a lot about bones. “That’s the strongest bone in the body, and it broke so easily.” The fragility
of Giana’s bone, and skin pigment marks known as “café au
lait” spots, led Stanford pathologist Jesse McKenney, MD,
to make the rare diagnosis of Jaffe-Campanacci syndrome.
Jaffe-Campanacci can include a range of symptoms, from
non-ossifying fibromas and café au lait spots — both of
which Giana had — to intellectual impairment, eye and heart
malformations, failure of one or both testicles to descend in
boys, and, in both sexes, diminished or absent sex hormone
production that can result in infertility. “Fortunately,” says
Greg, “Giana didn’t seem to have these other aspects of the
syndrome.”
Giana needed two repairs: to have her broken left femur
set and her left tibia lengthened and straightened. Although
this would not make her bones less fragile or prone to breaking, it would make her more stable on her feet in a way that
shoe platforms could not. Her surgeon knew that these corrections would each take several months to heal, but would
require different approaches: for the femur, an internal fixator that would be bolted directly alongside the bone; for the
tibia, the Taylor Spatial Frame, which could lengthen and
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STANFOR D CHIL DR E N’ S HEALTH; GRE G BR OWN ; OPPOSITE : SMI TH & NEPHE W
GIANA’S X-RAYS AT TWO MONTHS (LEFT) AND SEVEN MONTHS AFTER LENGTHENING BEGAN. RIGHT: WEARING THE FIXATOR.
With the top ring affixed, Young set about cutting the tibstraighten at the same time. He explained the process. Then
it was up to the family to decide whether to do both repairs at ia, making two 1- to 1.5-centimeter incisions about an inch
the same time. “I told them I would be there for them every apart, halfway between the top and bottom of the frame. He
step of the way,” says Young, a clinical assistant professor of then passed a wire, called a Gigli saw, through one incision,
into Giana’s leg, circling most of the bone, and back out the
orthopaedic surgery at Stanford.
“We could have started the lengthening right then,” other incision. “Using that wire like a cheese slicer,” Young
says Suki. “But mentally we didn’t have our heads around explains, “I cut the bone, sawing back and forth. We avoid
using a motorized saw because the heat can burn and kill the
this yet.”
Giana’s parents decided to let her femur heal first — which bone cells, effectively cauterizing the areas we need to heal.”
would take about a year — and then begin the lengthening Around every bone is a thin membrane called the periosteum
— meaning, literally, “around the bone” — which Young was
and straightening process the following summer.
“Between two and seven people per 10,000 in the United careful to keep in place. “It creates a safe boundary and is
States are affected by longitudinal deficiencies,” says Young, important for the bone healing as well.”
Young completed half the cut, affixed the rest of the
referring to conditions of unequal limb length. But the Tayframe,
then finished cutting with the bone fully stabilized
lor Spatial Frame is used for a variety of conditions, he exby the frame. He also placed a second frame on
plains, including deformities that happen after a
Giana’s foot to support her ankle. The resulting
bone break or injury, such as when bone growth
apparatus looked like the steel frame of a giant,
stops, when there is bone loss, or when a broken
open-air boot.
bone heals incorrectly (also called “malunion”).
Although Giana didn’t have the full spectrum
Orthopaedic surgeons also use the frame to heal
of symptoms often seen with Jaffe-Campanacci
limb deformities caused by infection, which
syndrome, she was extremely sensitive to pain.
can cause bones to stop growing or grow at the
WE B E X T RA
She spent a few nights recovering at the hospiwrong angle, or cause areas of bone loss. Some
Watch our
tal, but at home the pain was unbearable. “She
surgeons use the frame to extend limbs for peo3-D simulation of how
an external fixator
didn’t leave her bed for five days,” says Greg.
ple with achondroplasia, also known as dwarflengthens and
“We were supposed to be able to move her, but
ism. In California, Young says, only a handful
straightens bones.
she was in so much pain that we couldn’t.” She’d
of surgeons are trained to use the spatial frame,
http://stan.md/1udPa5M
reached her limit on pain medications, and they
and even fewer use it on children.
didn’t seem to be working. Suki and Greg were
“Approximately 1 percent of surgeons nationally are qualified to use the Taylor Spatial Frame, with deeply concerned, so they called Young, who did what few
the community growing slowly given what it enables the sur- surgeons are known to do: He went to Giana’s house to asgeon to address,” says Mark Waugh, vice president, extremi- sess her, and helped the family decide to bring her back to
ties and limb restoration for Smith & Nephew, the company the hospital.
“I’ll always thank him for that,” says Suki. “He knew what
that distributes the device. “It’s not a surgery you do and step
away from,” he adds. “Surgeons tend to build a relationship was good for that child.”
That night, Young connected the two braces — the one
with the patient and their family given the interactive nature
on Giana’s foot and the one on her tibia bone — which he
of the healing process.”
On July 12, 2013, Giana went into surgery. Young had al- had originally left separated to allow her ankle to move. Conready planned where to affix the frame, and where to cut her necting them relieved the pressure on Giana’s ankle. “Once
tibia to minimize complications from her bone disease. Once that was fixed, it seemed to help,” says Greg.
Greg, Suki and Giana all learned how to turn the struts
Giana was asleep and anesthetized, Young cleaned her leg and
placed a 1.8-millimeter stainless steel wire — called the refer- to the prescription settings for each day. “After the first two
ence wire — through her leg and bone. This wire served as a weeks, Giana didn’t let anybody else turn the struts. She had
guide for the most important part of the frame: the reference to turn them herself,” says Suki. “She had two little wrenchring. Acting as the point of origin for all the measurements that es, like they were made for kids’ hands. Every day at a certain
would go into the prescription, the reference ring also served as time, she would turn them, then mark the paper with a little
the top of the frame. Young further secured the ring with three colored pencil. She never complained, just got on and did it.”
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Surgeons at work
HEALING
WOUNDS
TH E F IR ST T IM E DAVID K AU FM AN SAW A H YP E RBA R IC CHA MB ER HE THOUGHT IT WAS THE SCA R IEST THIN G HE’D EV ER
S E EN . A LT H O U G H TH E M AC H INE D ID N’T LO O K E SPECIA LLY FR IGHTEN IN G — A CLEA R -WA LLED CYLIN DER WITH EN OUGH
RO O M FO R A LO NG BE D AND A VIE W O F A P ER SON A L MOVIE SCR EEN — IT WAS THE LAST STOP IN A N EIGH T- MON T H
E F FO RT TO H E A L A STU BBO RN FO OT WO U ND. IF THIS TR EATMEN T DIDN ’T WOR K, HE MIGHT LOSE A N OTHE R TOE. OR
MAY B E E V E N H IS WH O LE FO OT. TH E CH AM BE R REPR ESEN TED THE ON LY THIN G B ETWEEN HIM A N D A MPUTAT I ON . T HAT
S C A R E D H IM A LOT. • “It did take some getting used to,” says Kaufman about the treatment chamber. “You’re all alone once
they slide you in and lock the door. Then your ears start to ring when the pressure changes and they add the oxygen.” • Although the hyperbaric chamber treatment was designed to save deep-sea divers from a deadly condition called the bends, it can
help landlubbers too. By running pure oxygen in the chamber — room air is mostly nitrogen and has only about 21 percent
oxygen — red blood cells can pick up more oxygen to deliver to the rest of the body. For wounds that aren’t recovering, that extra
oxygen boosts new blood vessel growth to help old wounds heal. • Getting old wounds to heal is a big problem. In the United
States, about 6.5 million patients suffer from persistent wounds — from bedsores to burns. Experts anticipate those numbers will
only rise as the three major demographic groups that suffer from non-healing wounds are also expected to grow: people who
have diabetes, are obese or are over 65. More than $50 billion — at least 10 times the yearly budget for the World Health Organization — is estimated to be spent annually on managing wounds, according to an analysis of data from the U.S. Wound Registry. Most of the treatments, like the hyperbaric chamber, have been in use for decades. • “The problem with wound healing
CLOSING THE GAP
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is that it’s been a backwater of medicine — a lot of snake oil and
poultices — with no evidence-based medicine,” says Geoffrey
Gurtner, MD, a professor of surgery at the Stanford School of
Medicine. But that appears to be changing. Wound healing
as a medical specialty and as a subject of medical research is
coming of age. Ironically, the old-fangled hyperbaric chamber is part of the reason that change is coming.
Throughout the United States, wound-care centers are
popping up, with about 1,500 of these treatment centers nationwide. Housing technology like hyperbaric chambers and
a spectrum of specialists — from surgeons to infectious disease experts — these centers give patients a place to get comprehensive care for wounds. Revenue more than tripled over
three years for Healogics Inc., which operates 540 woundcare centers across the country: from $75.4 million in 2009
to $271.5 million by 2012. Bellevue, Wash.,-based Accelecare has opened about 25 new wound-care centers every year,
going from zero to 120 since launching in 2008, says Thom
Herrmann, senior vice president of business development.
Still, there’s room for more: Only about a third of U.S. hospitals have a physician-led wound-care center, according to
Jeff Nelson, president of Healogics.
In September, Stanford plans to open its own wound-care
center, including a hyperbaric chamber — in partnership
with Healogics. Stanford physicians will provide care while
the company provides business management expertise and
services such as hyperbaric equipment, staffing and training.
But unlike most wound-care centers, Stanford’s will be a site
not only for care but for research and training.
The front lines of wound care and research focus on diabetics like Kaufman because long-standing diabetic ulcers
are the most common, most expensive and most notoriously difficult wounds to heal. “For many diabetic patients
the medical clinic is a revolving door,” says Ronald Dalman,
MD, chief of Stanford’s Division of Vascular Surgery.
The more doctors understand how skin heals — or
doesn’t — the better they’ll be able to help people having
trouble recovering from wounds, such as cancer patients
getting radiation therapy or burn victims. If the hardest-toheal wounds can be improved, then those benefits will trickle
down to everyone else.
S K I N R E PA I R K E E P S U S W H O L E
W H E N T H E SK IN IS INJ U RE D — W H E TH E R BY ACCIDEN TA L
TR AU M A , SU R G IC A L INTENTIO N O R ILLNESS — THE B ODY
up to start healing immediately. A call to
arms signals the start of an orderly process involving all sorts
of cells that guide an influx of new blood vessels, tamp down
U SUA L LY R A M P S
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infection, build the scaffolding for new skin growth and ultimately lay down a new barrier to the outside world.
If our skin is working, it’s a multilayered shield that can
mend any chink in our armor. But when the skin’s healing
ability goes awry, it can put the health of our whole body at
risk. Unresolved wounds are a breach in the body’s defense
system: a painful portal for infections that can invade the rest
of the body — sometimes with life-threatening consequences.
No one appreciates that fact better than Kaufman, who
has dealt with diabetes for 20 years. When glucose stays too
high in the bloodstream, it blocks skin cells’ ability to repair
themselves and weakens the white blood cells that fight off
infections. That slow healing coupled with poor circulation
and loss of a sensation in the lower legs — two other common problems with diabetes — can lead to the loss of toes,
feet or even limbs. Diabetes is the reason behind most leg
amputations in the United States, and foot ulcers are a big,
red warning flag. These wounds presage more than threequarters of diabetes-related amputations, according to the
American Podiatric Medical Association.
Kaufman, 62, never had a problem with wounds until he
suffered a stroke in 2009. Then he lost much of the movement on his right side. With less activity, ulcers started showing up on his left foot, prompting his podiatrist to refer him
to a surgeon. “But the first surgeon wanted to take off all my
toes right away,” says Kaufman. He’d already lost one toe
from a previous infection and the surgery was intended to
save the rest of the foot. “I was only having trouble with my
pinkie toe then. So that didn’t sound like such a good idea.”
The next physician he met was Dalman, a man Kaufman
credits with keeping him on his feet.
N E W WAY S T O H E A L N E E D E D
TO STAVE OFF SURGERY FOR A TOE AMPUTATION, KAUFMAN
FIRST UNDERWENT A SUCCESSFUL PROCEDURE TO IMPROVE
Then Dalman recommended a
series of hyperbaric treatments —
­­ at a non-Stanford site, as
Stanford had no such facility at that time. Using multiple
approaches is often essential to manage complex wounds,
says Dalman. The high-oxygen treatment was the last little
push toward healing that Kaufman needed, but it isn’t an
option for everyone. With chamber pressures that hit more
than twice the normal atmospheric pressure, patients with
congestive heart failure or lung disease would fare worse
than their wounds. Newer treatments have been developed, such as skin substitutes and using suction to improve
circulation, but more is needed.
“It’s like the early days of infectious disease where simple
BLOOD FLOW TO HIS FOOT.
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hand washing went a long way to prevent disease, but people
still needed antibiotics. We’re in the same place with wound
healing with diabetics; we tell people to watch their feet so we
can catch ulcers in the early stages, but they still get chronic
wounds that need treatment,” says Gurtner.
Spurred by the plight of burn patients with debilitating
scars, Gurtner first took a surface approach to the problem of
wounds: He wanted to help people heal without thick scars.
After studying the problem with biomechanical engineers,
Gurtner led a team that developed a “stress shield” to reduce
surgical scars. Since tension drives the skin to lay down thicker tissue, they designed a device to keep tension from pulling
on the wound’s edges. Although the technique works well for
some patients, such as those with surgical incisions, it didn’t
help the burn patients. But it was a step in the right direction.
hydrogel matrices were made to act just like the skin of a
developing fetus. They look like a dry wafer, but can be rehydrated with a fluid containing stem cells, and then added
to the wound.
Early test results show these hydrogels accelerate wound
healing. Now, the researchers are figuring out the best source
of cells: fat, bone marrow or other sources. In the next round
of clinical trials, in which Gurtner hopes to start enrolling
patients before the end of this year, the hydrogel matrices
will be tested on diabetic foot ulcers.
But ultimately these stem cell sponges are intended to
help heal any chronic wound. It could be the perfect personal
bandage if Gurtner’s team learns how to seed the hydrogel
with whatever type of tissue needs regrowing. Skull wound?
Add early bone cells. And some types of cells might be guid-
‘WHY WOULD THE SAME DNA
HEAL WITHOUT A SCAR WHEN YOU’RE
IN THE WOMB AND THEN HEAL WITH A SCAR FOR
T H E W H O L E R E S T O F YO U R L I F E ? ’
To find new ways of preventing scars, Michael Longaker, MD, director of the Stanford Program in Regenerative
Medicine, dug deeper under the skin for answers. His work
is driven by one of the major mysteries of skin healing: In the
womb, we can heal without scars — right up until the third
trimester. “Why would the same DNA heal without a scar
when you’re in the womb and then heal with a scar for the
whole rest of your life?” he asks.
That question focused his attention on stem cells — the
cells that are blank slates until called to do a more specialized
job, such as becoming a cell that makes up bones or heart
muscle. Or scars.
“Maybe the rapid restoration of tissue — a scar — was
an advantage if it kept you from bleeding to death or being
eaten by a saber-toothed tiger,” says Longaker. “But scar tissue isn’t always good. If we can figure out how to knock down
the cells that make scars but still recruit cells that make blood
vessels, then we could have scarless healing.”
I T TA K E S B L O O D T O H E A L
BLO O D V E SS E L S A RE TH E P IP E LINES TH RO U GH WHICH A LL
and start rebuilding after a skin defect. But injuries can destroy blood vessels.
So Longaker, Gurtner and a group of their Stanford
colleagues tried another approach to getting those growth
factors where they were needed: stem cell sponges. These
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ed to become other types. In the right matrix, for instance,
fat cells (which have the advantage of being relatively easily
accessible) might be persuaded to become new cardiac cells.
It may sound like a far-fetched treatment plan but the underlying science is compelling enough for the Department
of Defense to fund some of this research. “It only makes
sense,” says Gurtner. “More of our soldiers are coming home
wounded. In World War II, three were wounded for every
one lost in battle. In Afghanistan, 13 soldiers are wounded
for every one killed.”
Researchers around the country are trying other strategies
to rebuild blood vessels. One example is Robert Kirsner, MD,
PhD, vice chair of dermatology and cutaneous surgery at the
University of Miami Miller School of Medicine, is studying a
spray that delivers blood vessel and other growth factors directly on the wound surface — sort of like spreading fertilizer
to get a healthier lawn. With this foaming gel, a combination
of keratinocytes from the top layer of skin and fibroblasts from
the layer below it, early studies showed that patients with venous leg ulcers healed an average of three weeks faster than
those treated by standard care.
“The stakes are high,” says Kirsner. “For some of the
chronic wounds we treat, if we fail to heal these ulcers then
patients have close to 50 percent mortality in five years —
that’s worse than the rates for someone with breast cancer.”
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O
NE DAY THIS SPRING, STANFORD ANESTHESI-
OLOGIST DIVYA CHANDER, MD, PHD, DONNED HER SCRUBS, WASHED HER HANDS, AND WALKED INTO THE
OPERATING ROOM FOR A ROUTINE SURGERY. A RESIDENT ANESTHESIOLOGIST-IN-TRAINING HAD ALREADY
STUCK FLAT, ROUND ELECTRODES ON THE PATIENT’S FOREHEAD, AND WIRES SNAKED FROM THE ELEC-
Chander glanced at the
machine’s readout, a mountainous terrain of lines pulsing up and down, representing the complexity of information zipping
between cells in the brain. These EEG patterns didn’t look like those of an awake person, she thought to herself. • “Oh, have
you pushed the anesthetics already?” she asked the resident. He shook his head. Chander frowned, then reached down and
shook the patient’s shoulder. Suddenly, the man’s eyes snapped open and the EEG returned to a more expected pattern. He’d
been napping. • A decade ago, it’s unlikely that any clinician could glance at the raw squiggly lines of an EEG readout and
determine whether a patient was awake or asleep, anesthetized or not. If they had an EEG machine in the operating room at
all — a trend that began in the mid-1990s — it likely displayed only some numbers. But now, many neuroscientists and anesthesiologists are tackling an area previously claimed only by philosophers: consciousness. Their research over the past dozen
years has begun to illuminate how the brain’s patterns of activity shift as a person’s awareness of their environment changes.
By bettering their ability to track consciousness, anesthesiologists hope they can learn how to detect when a patient loses
TRODES TO AN ELECTROENCEPHALOGRAPHY MACHINE BESIDE THE OPERATING TABLE.
By Sarah C. P. Williams
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and regains consciousness, fine-tune drug levels to optimize
individual patients’ sedation, and develop more effective and
safer anesthesia drugs.
Chander is among those who have immersed themselves
in the few measures of consciousness available, like EEG, to
get a grasp on what changes during sedation. Being under
general anesthesia, researchers like Chander have found,
closely resembles being in a deep sleep, hence her mistaken
assumption in the operating room. In both cases, neurons
have slowed their telltale rhythms and fallen into a more stereotyped pattern that prevents one region of the brain from
communicating well with other regions.
Consciousness is often defined as being awake, having
a sense of self, or an awareness of your surroundings. For
doctors, classic measures of
consciousness include testing
patients’ level of awareness
and attention, and asking them
whether they know the date
and where they are. But historically, the concept of consciousness has also had a more
spiritual definition — some
believe consciousness is unique
to humans; some link it to the
idea of a soul.
For many centuries, scientists and philosophers alike saw
consciousness as something to
ponder and discuss, but not
something that could be explicitly measured. For them,
consciousness was more than
a physical process. They believed that even if one could
re-create an entire brain from
scratch, a conscious being — with self-awareness and introspection — wouldn’t result because it would be missing
a soul. But as neuroscientists have developed new ways to
study what happens within brain cells when people engage
with their environment, they’ve noticed patterns — like
those Chander can see on an EEG readout — linking physical processes in the brain to consciousness.
“It is not that there was a single, dazzling neurobiological
experiment showing that consciousness is a biological phenomenon,” says Patricia Churchland, a neurophilosopher at
the University of California-San Diego, who regularly works
with neuroscientists and anesthesiologists to probe conscious-
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ness. “Instead, there has been an accumulation of important
results that collectively render that conclusion fairly obvious.”
Such realizations don’t just have implications in the
realm of anesthesia, but could lead to new ways to gauge
brain injuries, reverse comas, define sleep problems and
treat cognitive disorders.
T R AC K I N G CO N S C I O U S N E S S
By any definition of consciousness, there are countless ways
to lose it. Epileptic seizures, some recreational drugs and
many brain injuries knock people unconscious. But most of
those situations that cause diminished consciousness — head
trauma, for instance — are both unpredictable and dangerous and can’t be studied in a controlled way in a lab or hospital. Anesthesia, though, provides a perfect testing ground
for concepts of consciousness.
“There are very few situations where you can probe human consciousness except when
it is depressed,” says Chander.
“Anesthesia is one of the best
model systems we have because
we can both remove and restore consciousness with drugs
and we can study the loss of
consciousness in the absence of
brain damage.”
Typically, anesthesiologists
track sedated patients’ levels of
consciousness through crude,
indirect measures of bodily
function — during surgery,
they keep an eye on a patient’s
blood pressure and heart rate.
Although the EEG has been
around for the latter half of the 20th century, medical device
companies have only recently began promoting the use of
EEG in the operating room. In the early 1990s, companies
first developed machines designed specifically to monitor
anesthetized patients — they each developed their own proprietary formula that analyzes raw EEG readouts and spits
out a number indicating a patient’s depth of unconsciousness.
But anesthesiologists like Chander think the single number
is a poor measure of what’s happening clinically. The number, between 0 and 100 on most systems, involves a complex calculation that can take minutes to generate, making it
difficult to use for real-time decision making. It also doesn’t
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take into consideration the variety of drugs that can be used
— and that have varied effects on physiology, Chander says.
“That number doesn’t mean much during critical periods,” she says. “If you relied on the number to make clinical
decisions, you’d be in real trouble.” So most anesthesiologists, she says, don’t rely on EEG at all.
Chander — who already had a PhD in neuroscience before choosing anesthesia as her clinical specialty — thinks the
time is ripe, though, to start turning to raw EEG data to get a
more nuanced view of how consciousness changes during anesthesia. A few years ago, on the suggestion of a mentor and
colleague, she started displaying the raw waves of data rather
than the processed index number on the EEG machines of
every patient she puts under, a change that takes the simple
click of a button but is rare outside of research labs.
Over time, she began noticing particular patterns of brain
activity as a patient drifted in and out of consciousness and
as she administered different drugs. Now, she’s organizing
those observations into more concrete data on consciousness. Chander is interested in understanding what changes
take place in neural networks during changes in level of consciousness. If she can see them in real time on the EEG in
the operating room, that information may ultimately be used
by clinicians to monitor anesthetic depth. She and her colleagues are also finding that the way in which people emerge
from anesthesia may influence how they feel after surgery.
“Some people have a very gentle, easy wake-up from anesthesia and feel great,” she says. “Other people are very agitated, disoriented or in pain.”
But even if Chander nails down exactly what happens in
the brain as an anesthetic causes a patient to lose consciousness, or as the patient emerges back to consciousness again,
there’s no guarantee that the same changes occur when a person is made unconscious through other means.
“It’s clear that there’s no one switch that flips to go from
conscious to unconscious,” says Stanford anesthesiologist
Bruce MacIver, PhD. “All the ways you can lose consciousness — falling asleep or getting anesthesia or a head injury
— all have different underlying mechanisms.”
To aid in understanding the neural basis for some of these
consciousness state-switches, Chander has worked with Stanford professor of psychiatry and of bioengineering Karl Deisseroth, MD, PhD, a developer of a technique called optogenetics, and Stanford associate professor of psychiatry Luis
de Lecea, PhD, who uses optogenetics to study sleep. Using
genetically engineered mice with special light-sensitive proteins in their brain cells, researchers can control when different neurons fire by shining light on them. Chander is using
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optogenetics to control areas of the brain that she suspects
might play a role in consciousness. She can test whether firing certain neurons makes a mouse go from an unconscious
to conscious state — or vice versa.
“Optogenetics is the way I control the system, and EEG is
the readout device,” says Chander. The patterns she observes
in patients during anesthesia help inform which areas she studies in mice. She hasn’t published results yet, but thinks that
combining clinical data with the latest molecular approaches
— like optogenetics — will be key to discovering which neural
networks support the consciousness state of the brain.
BUILDING BETTER ANESTHETICS
As far back in history as ancient Egypt, healers searched
for drugs — from alcohol to opium to other herbs — that
would ease patients’ suffering during surgical procedures. By
the early 19th century, doctors had discovered mixtures of
natural compounds that would not only ease pain, but induce
temporary states of paralysis and unconsciousness. The use
of chloroform and barbital to sedate patients soon followed.
Through chance and happenstance, trial and error, the field
has settled on a handful of drugs that put patients into a deep,
but reversible, state of unconsciousness — somewhere between a normal night’s sleep and a coma.
Many of today’s drugs are derivatives of the compounds
that have been used for centuries, and none is as effective nor
as safe as doctors would like. One in 1,000 patients remembers parts of their surgery afterward, indicating that they had
some level of consciousness during it. And for some patients,
anesthetics cause plummeting blood pressure and the risk of
death. “Not a single one of these drugs has been designed
rationally to achieve any known mechanism or desired effect
in the brain,” MacIver says.
He thinks that by uncovering what defines consciousness
and unconsciousness he can design better anesthetics and
improve the tracking of a patient’s state while they’re under.
Anesthesiologists, he says, want to ensure that every patient
remains unconscious for the duration of a procedure, but
using the least amount of anesthetic possible. “There’s increasing evidence that the lighter we keep patients, the better
their speed of recovery,” he says.
To characterize different anesthetics and how to detect
the right dosage, MacIver’s lab administers the drugs to rats,
and uses EEG to observe what happens. They’ve pinpointed
a few key changes to the EEG that tend to happen at the
exact moment that rats from go from being able to respond
to a stimulus to being unresponsive.
But applying these data to the operating room is tricky.
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Interpreting the pulsating lines of raw EEG data on the spot
is a skill that few clinicians have. “An EEG is this weird, random, squiggly line that changes quite a bit from moment to
moment,” MacIver says. And like Chander, MacIver doesn’t
put much weight in the processed index numbers that EEG
machines display in most operating rooms. But while Chander thinks one solution is to teach more anesthesiologists to
read the raw form of the EEG data, MacIver and Chander
are also teaming up on another solution: an entirely new way
to display EEG data. “We’re using the exact same data that’s
been recorded for decades,” MacIver explains. “But we’re
finding new ways to visualize it.”
His EEG visualizations look like balls of yarn — the more
spherical they are, the more chaotic the brain’s signals are.
And chaos, in this case, means consciousness. “When a rat is
awake,” he says, “it’s a perfect sphere.” When a rat is unconscious, rather than a tight sphere, lines project far outward
from an oblong ball.
But neither Chander nor MacIver has achieved a perfect
method to track consciousness. Based on his data from rats,
“we can get about 80 or 90 percent accuracy in humans for
loss of consciousness,” MacIver says. “But we’d like that to be
100 percent. Already by tracking vital signs we can get better
than 90 percent accuracy.”
One step toward getting better, they say, is having the chance
to put patients under anesthesia at a much slower rate than is
usual during surgery. MacIver and Chander are currently recruiting participants for a study that will observe subtle EEG
changes in their brains as they’re very slowly anesthetized.
DIGGING DEEPER IN THE BRAIN
A few years ago, Brett Foster, PhD, was a graduate student
in Australia trying to understand how different anesthetics
and sedatives influence brain activity in different ways and
can make the EEG index numbers hard to interpret. Time
and time again, his results and his literature searches pointed
toward the importance of the midline parietal lobe — a region of the brain sandwiched in the center, between the two
halves, called hemispheres. But EEG can’t accurately record
the activity in the midline of the brain.
“Where the two hemispheres of the brain push up against
each other, the brain curves down between them,” Foster explains. “When you’re using electrodes on the scalp to record
activity, this valley is too deep. Any signal gets smeared and
smoothed out before it reaches the electrodes.”
But Foster learned that Stanford neurologist Josef Parvizi,
MD, PhD, was more accurately recording the activity in this
area of the brain in patients with epilepsy. In select patients
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with especially severe seizures, doctors implant electrodes in
their brains to determine where seizures are originating and
whether surgery can treat their epilepsy. But Parvizi, an associate professor of neurology, was also taking advantage of the
deep placement of these electrodes to study — with the patients’ permission — broader questions about brain activity.
With the electrodes, he could either stimulate select neurons
or record their activity. Foster saw Parvizi’s work as a perfect
inroad to the parietal lobe’s potential role in consciousness
and memory and joined his lab at Stanford as a postdoctoral
researcher.
Parvizi and Foster can’t knock their epilepsy patients unconscious, but they can study the activity in the brain’s midline as these patients perform simple tasks, recall events, tell
stories or go about their daily activities in the hospital. One
aspect of consciousness that they’re trying to study has to do
with attention — part of being conscious has to do with paying attention to your surroundings. Someone who is zoning
out in class can be said to have a different level of consciousness than someone listening to the professor’s every word
— though both are quite conscious. Parvizi and Foster are
observing how activity deep in the brain is different when
someone notices a stimulus compared with when they don’t.
Another aspect relates to memory — why does the midline
light up when someone is recalling the past, and how does
that relate to the fact that patients have no memory of their
time spent under anesthesia?
“For us, this is an opportunity to get measurements from
this hard-to-access part of the brain,” Foster says. “But what
we need to do is build up from very basic questions.”
Parvizi says the implanted electrodes offer far
more detail than previous methods, but technology still limits scientists’ understanding of the brain.
“We know that consciousness is likely mediated by many
regions of the brain and controlled by how those regions
are interacting,” he says. “Right now, we can’t simultaneously record from all over the brain at once. We have to
pick and choose what to look at.” But a new grant they’ve
received will let them focus on how the midline parietal
lobe communicates with other areas.
H U M A N S : CO N S C I O U S M AC H I N E S ?
If consciousness is viewed as a spectrum, then the study of
consciousness doesn’t just mean finding a single line that
people cross from conscious to unconscious. People in a
coma are less conscious than those asleep for the night;
people who are hyper-alert to their surroundings are more
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Surgeons at work
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HOSPITAL, BUT IN THE OR THE TEAM IN SUITE NO. 4 WAS WRAPPING UP A 12-HOUR ANEURYSM CLIPPING.
EVERYONE WAS SPENT BUT STILL FOCUSED. THEY BEGAN TO FALL INTO A RHYTHM, WHICH VISIBLY RECHARGED THE ENTIRE TEAM. Within 30 seconds, they were all operating from the same groove: Heads began to bob,
toes tapped, the scrub tech strummed his air guitar with a pair of forceps, and off to the side the circulating nurse did a little
Michael Jackson spin-a-roo as she notched up the music. • The OR can be a gnarly place. Same for the emergency room and
the catheterization lab. But in the OR, gnarly can go on for hours and hours and hours. Knowing how and when to tame the
tension is invaluable, and surgeons consider it an art form. • “It’s a fine balance,” says Gary Steinberg, MD, PhD, professor
and chair of neurosurgery at Stanford. “You relax people enough so that they can perform their best, but not so much that
they start missing details.” He says that Stanford’s OR is consciously working toward a more relaxed attitude, and that music
plays a big role. He shakes his head: “We never used to play music in the operating room when I was training.” • It was during
the ’80s that Steinberg went through his training at Stanford. In those days, the hierarchical mode of teaching was as much
a rite of passage as it was an education. Ridicule, hazing and tirades were par for the course. These days, the training leans
more toward team dynamics, building an esprit de corps. This is partially because the newer generation of surgeons seeks a
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more realistic work-life balance. “In the old days, you killed
yourself to be a doctor or a surgeon,” says assistant professor
of vascular surgery Venita Chandra, MD. “Everything else
was put on hold. Today, that’s no longer acceptable.”
Let’s backtrack 12 hours to the start of the procedure in
suite No. 4. Neurosurgery chief resident Anand Veeravagu,
MD, mulls over the music menu that will accompany this
long-haul procedure. To get the team teed up, he puts on
Pink’s Let’s Get This Party Started and it sparks the desired
effect. The anesthesiologist’s focus is on the patient, but you
can see he’s feeling the beat. Neurodiagnostic technologist
Jackie Varga two-steps around him, attaching electrodes to
the patient’s legs. A nurse rhythmically swabs the patient’s
head with antiseptic, and the circulating nurse glides in and
around them all. This group
works together so frequently
that the bustle around the table looks choreographed. And
even though they’re all grooving to the tunes, the care and
safety of the patient is deeply
ingrained and permanently
paramount. Abruptly, Veeravagu turns off the music and
the sudden silence grabs everyone’s attention. He calls for the
timeout and review of the surgical checklist, procedures that
happen before every surgery at
Stanford.
Step by step, they verify
that everything necessary for
the patient and the surgery
is at hand. Everyone, regardless of seniority or position, is
encouraged to ask questions
or voice concerns. Then, a quick round of introductions
— including the surgical team and observers alike — concludes the timeout. The timeout and checklist were instituted about seven years ago with the goal of improving
patient safety. But one can see how they also knit the group
together, bolstering team dynamics.
With his scalpel, Veeravagu makes the first incision,
then fires up the bovie, an instrument that cauterizes as
it cuts. It makes a staticky hum, and a thread of smoke
spirals up from the patient, producing the vaguely offputting smell of burning flesh. The visitors around the
periphery watch with arms folded, trying to ignore the
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chilly air, but the team around the table is oblivious to
the temperature. They’re focused on the procedure as
they stand under bright lights, swaddled in blue surgical gowns and gloves atop the standard-issue blue
scrubs worn by everyone (other than the patient) who
enters Stanford’s OR.
Not all OR attire is blue, though. Clogs have been the
OR’s go-to shoe for decades, and Chandra is sporting a new
hot-pink pair. She says she got them “just to have a little
fun.” Not too good for rock climbing, but their generous
arch support makes them great for long bouts of standing
and toe-tapping to the tunes.
As for the hats everyone in the OR must wear to cover
their hair, colorful toppers can be a tip-off to the personality of the soul below. Varga,
the neurodiagnostic tech and
a kind soul, is a serial hatter.
The ubiquitous shower-cap
style is good for covering
long hair, but bad for flattering the face. Varga decided to
make her own hats and soon
co-workers began to request
them. Now she makes them as
gifts. “I go crazy with all the
fabric choices. When I see a
fabric, and it reminds me of
a person, I think: Well, they
just have to have a hat.” She
guesses she’s made at least 200
over the years.
In suite No. 4, it’s the seventh hour, and the action has
ebbed. Now, the surgeons can
finally step out to give their
kidneys a break. The music
picks up, as does the conversation. There’s playful banter,
and wisecracks zing between Veeravagu and scrub tech Chip
Hamilton. Hamilton has worked closely with the surgeons
for nine years, anticipating their next moves, being at the
ready with the proper instrument, device or dressing. He
says the OR is much less intense than it once was. “There’s
no longer room for aggression or embarrassment.” He
smiles and adds, “it’s more like family now.”
He calls to a nurse who’s fiddling with the music, “Cue
up Sister Sledge!” and he goes back to ribbing Veeravagu. In
the background: We are family. Get up everybody and sing.... SM
—Contact M.A. Malone at [email protected]
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Six or so years ago, Frank Longo, MD, PhD, Stanford’s chair of neurology and neurological sciences, was optimistic that a treatment for Alzheimer’s disease was on its way. More than a decade
earlier, pharmaceutical companies had begun testing drugs to eradicate one of its hallmark signs
— clumps of protein sprinkled randomly throughout the brain. The drugs were antibodies that
bind the protein, called beta amyloid, or A-beta for short. • “They poured a lot of money into clinical trials
of these antibodies in Alzheimer’s patients,” says Longo. “And by around five years ago, with the conclusion of early-stage trials, it
looked like they might succeed. So, many in the field — including me — had some guarded optimism that when the pivotal phase-3
trials were completed, this approach would have at least some beneficial effect.” • On the order of 30 million people worldwide,
including more than 5 million Americans, have Alzheimer’s, the most common form of dementia, which raids the brain and steals
a person’s ability to remember, reason and imagine. Barring substantial progress in curing or preventing it, Alzheimer’s will affect 16 million U.S. residents by 2050, according to the Alzheimer’s Association. The group also reports that the disease is now
the nation’s most expensive, costing over $200 billion a year. Recent analyses suggest it may be as great a killer as cancer or heart
disease. • It’s not really clear what causes the disease, and even rendering a diagnosis involves some guesswork. Genetic factors
have been shown to contribute to the likelihood of getting it, but none among them comes close to fully predicting or explaining
its onset and progression. What’s known is that the diseased brain is characterized by the protein clumps outside of nerve cells and
tangles of fibrous filaments within them, accompanied by an accelerating die-off of those nerve cells. And that there is no cure.
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So it was unfortunate that three separate phase-3 trials
testing the antibody strategy all failed to have any therapeutic
effect on cognition. “I’d like to have something better to offer my patients,” says Longo, who directs the Stanford Center for Memory Disorders. “It’s profoundly disappointing
when that doesn’t happen.”
In the wake of this disappointment, research to understand Alzheimer’s has shifted focus. Instead of trying to address signs and symptoms seen in the end stage of disease,
researchers are looking at what goes wrong much earlier in
Alzheimer’s. Their insights have yielded promising new imaging techniques and new targets for therapeutic drugs, with
at least a couple being tested by startup companies Stanford
researchers have spun off.
WHEN THE BRAIN’S BRAKES
LOCK UP
“By the time visible symptoms of dementia appear and a patient first sees a doctor about it, this process has been under
way for years,” says Carla Shatz, PhD, a professor of neurobiol-
physiological basis of learning, ruminating and daydreaming;
of remembering, forgetting and regretting.
But too-much, too-fast alterations in synaptic size and
strength could be deleterious. They could, for example, trigger epilepsy. It’s good to have that brake pedal.
Shatz recently found that PirB-deficient mice, even when
they’re carrying two mutations that strongly predispose people to Alzheimer’s, develop no symptoms of Alzheimer’s. They
get through mazes just fine. Their memories seem intact.
When she and her labmates discovered that small, stillsoluble clusters of the infamous A-beta peptide bind very
strongly to PirB and that, moreover, PirB concentrated at
synapses, she got downright excited. Further experimentation showed that this binding led synapses to break down.
Shatz’s lab recently identified the human counterpart to
PirB, called LilrB2. If soluble A-beta is triggering synaptic
loss long before amyloid plaques become visible, maybe inhibiting the A-beta/LilrB2 binding or the chain reaction it
sets off could be therapeutic early on, possibly protecting
against cognitive deficits.
ogy and of biology and the director of Bio-X, Stanford’s inter-
A few promising early
signals of impending Alzheimer’s do exist — for example,
changes in amounts and ratios of certain chemicals in spinal
fluid, or the changes observed by investigators via functional
brain imaging. But wide-scale spinal taps or brain scans are
hardly efficient ways to screen large numbers of people in
the hopes of initiating therapeutic interventions earlier — if
indeed there were something to intervene with. What would
be great would be to find a molecular mechanism that not
only provides a way to detect the approach of Alzheimer’s but
also offers a window into the disease process.
Shatz’s recent work has turned up an unexpected player —
a molecule once thought to be important only in the immune
system but discovered by Shatz over a decade ago to moonlight in the brain. The molecule, called PirB, is a protein that
acts like a brake dialing down the ferocity of the immune
response — important if, for example, autoimmunity is to
be avoided. Shatz found that in the brain PirB appears to
serve as a brake on a different vehicle altogether: the synapse.
Synapses are discrete, tiny but critical contact points at which
each nerve cell conveys signals to others. Your memories are
stored at brain circuits’ synapses. A single nerve cell can sport
10,000 or more synapses, each connecting with a different
partner nerve cell. In response to our experience and development, synapses are in a throbbing state of flux: being born,
enlarging and strengthening, diminishing and weakening,
or disappearing altogether. This relentless fidgeting is the
disciplinary bioscience consortium. •
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THE IMMUNE CONNECTION
The brain doesn’t exist in a bottle or a vacuum. It dwells within
the body, where it is in constant conversation with the body’s
other great communicators — notably the immune and endo-
In August 2013, Ben Barres, PhD, professor
and chair of neurobiology, published a study in the Journal
of Neuroscience revealing that another protein more typically
associated with immune function may be a major early player
in neurodegenerative processes.
Examining brains from young and old mice and humans,
Barres and his team observed a 300-fold uptick in the prevalence of a particular protein called C1q. “No other protein
has ever been shown to increase nearly so profoundly with
normal brain aging,” he says. And guess what? This accumulation is concentrated at synapses. The buildup begins
precisely in portions of the brain (such as the hippocampus)
that are the most vulnerable to early neurodegeneration in
Alzheimer’s disease. As the brain ages, these C1q deposits
spread to synapses throughout the brain.
C1q is no garden-variety protein. As every immunologist knows, C1q bats first on a 20-member team of immuneresponse-triggering proteins, collectively called the complement system. Abundant in circulating blood, C1q can cling
to bacteria or bits of our own dead or dying cells, initiating a
molecular chain reaction called the complement cascade. One
by one, each of the system’s other proteins gloms on, coating
the offending cell or dollop of debris and drawing the atten-
crine systems.
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FOR ALZHEIMER’S?
AT AG E 65,
a woman’s chances of incurring Al-
zheimer’s disease are one in six: nearly twice
most half of those diagnosed with Alzheimer’s
onset of menopause, when intrinsic estradiol
don’t carry any copies of ApoE4 at all.
production dives abruptly, suffer substantially
that of a man’s estimated one in 11 likelihood.
In a study published in Annals of Neurol-
less deterioration in key brain areas that, other
New studies of the strongest known genetic
ogy in April, Greicius and his colleagues ex-
studies have shown, faithfully predict clinically
risk factor for Alzheimer’s — a gene called
amined clinical and biochemical data on some
significant dementia by years and decades.
ApoE4 — provide insight into why women are
8,000 older people, many of whom showed no
So is estrogen replacement the way to pro-
more at risk and hints for a solution.
initial signs of dementia, and concluded that
tect women from Alzheimer’s? It is for some,
the increased Alzheimer’s risk conferred upon
says Rasgon, but not all.
In general, people carrying a copy of
ApoE4 are at a heightened risk — about
ApoE4 carriers is much greater in women.
Estradiol’s effects on the body aren’t en-
two- to four-fold — of developing Alzheim-
That finding may have clinical ramifica-
tirely benign. For example, she notes, expo-
er’s. Those with two gene copies encoding
tions. Another new brain-imaging study led
sure to the hormone raises the risk of breast
ApoE4 (one inherited from dad, one from
by Natalie Rasgon, MD, PhD, professor of
and uterine cancer. “Perimenopausal women
mom) are at 10-fold risk and are likely to
psychiatry and behavioral sciences and direc-
with risk factors for dementia should talk to
start showing symptoms earlier in life than
tor of the Stanford Center for Neuroscience in
their doctors about whether estradiol-based
most others.
Women’s Health, followed women who were
hormone therapy makes sense,” she says.
But there’s obviously more to Alzheimer’s
at heightened Alzheimer’s risk because, for ex-
If these results wind up being replicated
than just having that gene version. “An ApoE4
ample, they had at least one copy of ApoE4 or
in a large sample of postmenopausal women
carrier can live to be 90 and still not get Al-
a family history of the disease. Rasgon’s study
not at risk for dementia, estradiol-based hor-
zheimer’s,” says assistant professor of neurolo-
found that those who adopt estrogen-replace-
mone therapy could become more broadly
gy Mike Greicius, MD, medical director of the
ment therapy consisting solely of estradiol (the
a treatment of choice to preserve optimal
Stanford Center for Memory Disorders, and al-
dominant female hormone) shortly after the
brain aging, she says.
tion of omnivorous immune cells that gobble up the target.
The brain has its own set of immune cells, called microglia,
which can secrete C1q. Other cells called astrocytes secrete
the rest of C1q’s complement-system “teammates.” The two
cell types work analogously to the two tubes of an epoxy kit, in
which one tube contains the resin, the other a catalyst.
Every cell type in the body except one — nerve cells —
produces numerous substances that inhibit different stages
of the complement cascade (which would explain why the
complement cascade isn’t typically activated by events transpiring within those cells).
Barres believes that in the normal aging brain, C1q, but
not the other protein components of the complement system,
gradually becomes highly prevalent at synapses. By itself, this
C1q buildup doesn’t trigger wholesale synapse destruction,
or even much affect synaptic health. But it does leave the
aging brain’s synapses perched on the brink of catastrophe.
An event such as brain trauma, a bad case of pneumonia or
perhaps a series of tiny strokes could incite astrocytes — the
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second tube in the epoxy kit — to start squirting out the
other complement-system proteins required for synapse loss.
Barres says the brains of Alzheimer’s patients show a 70-fold
increase in levels of complement-cascade activity.
In our early development, our brains sprout a surplus of
synaptic connections. This redundancy allows for myriad
potential brain circuits, but as the organism begins logging
life experiences, the plethora of synapses becomes an embarrassment of riches. Within any single circuit, an excess of
extraneous synaptic connections means noise in the system.
Like a sculptor chiseling a statue of cognitive efficiency from
raw marble, the brain has tools, including the complement
system, for pruning unused or misused synapses during fetal
and childhood development. Barres thinks the complement
cascade ordinarily becomes quiescent in the adult brain after
actively assisting in the “pruning” of redundant or counterproductive synapses during early development, but can get
induced by a variety of inflammatory events to turn on again.
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EARLY A YEAR HAS PASSED, AND THE
U.S. SURGEON GENERAL POST IS STILL VACANT. DOES IT MATTER? ASSOCIATED PRESS MEDICAL REPORTER MIKE STOBBE’S NEW BOOK, SURGEON GENERAL’S WARNING [UNIVERSITY OF CALIFORNIA PRESS, JUNE
2014], EXPLAINS WHY THAT QUESTION IS SO HARD TO ANSWER. HIS LOOK AT THE HISTORY OF THE POSI-
from having a powerful surgeon general. It also examines how politics are draining that power. • But don’t take our word for it.
In these three excerpts from the first chapter, read what Stobbe has to say about the position’s decline and its sequelae.
TION AND THE PERSONALITIES WHO FILLED IT SHOWS THE GOOD THAT’S COME TO AMERICA
took her place in front of dark-velvet curtains, set her smile and waited. • The scene was a bit like
“pictures with Santa” at a busy shopping mall on the Saturday before Christmas. More than 150 people patiently stood in
line to have their photo taken with Benjamin, some with emotions akin to the awe of a child about to meet St. Nicholas.
They craned their necks to see her up ahead; some were even a little giggly. Benjamin’s helpers, wearing uniforms like
hers, managed the crowd. • But the similarities stopped there. This was weeks after the holiday (Jan. 11, 2010, to be exact).
These were adults standing in line. The venue was the foyer of a federal building in downtown Washington, D.C. And this
wasn’t Kris Kringle they were waiting to see; it was the new U.S. surgeon general. • Minutes earlier, in a packed, 625-seat
auditorium, Benjamin had been formally sworn in as the nation’s 18th surgeon general. It had been an unusually florid affair, even by Washington’s standards. Rows of federal health officials were dressed in the formal, militaristic uniforms of the
commissioned Corps of the U.S. Public Health Service. Some formed a saluting gauntlet that Benjamin passed through at
the end. A passerby might have mistaken the event for some kind of war-hero homage. • Benjamin had many supporters
there that day, and they were thrilled. • “It’s wonderful to know that someone whose values you respect is in such a posiREGINA BENJAMIN
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tion of leadership,” said Brenda Smith, an American University law professor standing in line with a group of friends.
“This is a great day for our state. For the world,” said
Betty Ruth Speir, an elderly gynecologist who, like Benjamin, was from Alabama.
Was it, though?
The surgeon general is indeed a public health celebrity, a post
rooted in a rich history and automatically held in high esteem.
Surgeon general reports remain hallmark documents in our society, cited in everything from student term papers to legislative
policy debates. Surgeon general warnings are fixtures on magazine liquor ads and cigarette packaging. Polls assessing the surgeon general’s credibility award the position higher marks than
most other government health officials. Indeed, the surgeon
general is commonly perceived (or, rather, misperceived) to be the government official responsible
for the health and wellbeing of the general public. The surgeon general
stars in public service announcement commercials
and speaks frequently at
university commencements and national conferences. The uniform
and title still conjure importance and wisdom, and
— for some Americans
— a belief that there is still
such a thing as a government health official who
will level with the public when other bureaucrats won’t.
Some of that aura comes from dewy memories of the surgeon general’s power, independence and integrity as it was
many decades ago (when the federal health bureaucracy was
smaller). “He did not have to kowtow to the administration,”
said Daniel Whiteside, a dentist who served for years in the
Public Health Service. “He could say, ‘I don’t care what the
administration’s policy is on any health issue. I’m going to tell
you what is in the best interest of the American public, so far as
a health issue is concerned. I don’t care who likes it. I don’t care
who doesn’t like it. I’m here for four years and you can’t touch
me.’ And we had surgeon generals who did that; I mean, who
went up against the administration and said, ‘Kiss off.’”
Whiteside was speaking mainly about the men who held
the position in the early 20th century — the long-ago kings
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of U.S. public health who served multiple terms while presidents came and went. But the perception that surgeons general
are science-above-politics monarchs, acting as the uncensored
health consciences of the nation, occasionally has resurfaced.
Jesse Steinfeld, who held the job in the early 1970s, angered
Nixon administration officials by attacking the cigarette and
television industries. C. Everett Koop, in place through most
of the 1980s, led a benevolent education campaign on the
emerging AIDS epidemic when some Reagan White House
officials disdainfully considered it a gay disease. Joycelyn Elders, surgeon general in the early 1990s, dismayed the Clinton
administration with her frank remarks about whether to legalize marijuana or teach kids to masturbate.
But in truth, tolerance for outspoken surgeons general
has always been limited.
Elders was fired. Steinfeld was forced to resign
early. Even the powerful
surgeons general of old
were careful not to cross
certain political overlords. An example: Hugh
Cumming, who held the
job from 1920 to 1936,
was considered one of
the most powerful surgeons general of all time.
In 1925, after a rash of
industrial worker poisonings tied to leaded gasoline, Cumming was publicly pressured to look
into it. But he declined to
take any action until he first discussed it with Secretary of the
Treasury Andrew Mellon — whose family had financial interests in the oil industry. (Mellon, to his credit, recused himself
and told Cumming to use his own judgment.)
Surgeon General’s Warning is a brief history of the office
that includes the proud moments and the despicable ones,
the perception and realities, the heroes and the scoundrels.
The book explains how the surgeon general became the most
powerful and influential public health officer in the country
and how those powers were later stripped away. It discusses
the unique bully-pulpit role the post retained, and the prowess of some surgeons general in using that pulpit and the
meekness of others. It examines how the Office of the Surgeon General reached its current nadir. And it concludes that
it no longer makes sense to have a surgeon general.
4 7
taken the surgeon general’s place in the spotlight have tended
to walk a politically correct line and to steer clear of controversies that might trigger “nanny state” complaints that the government is meddling in the lives of individuals. They almost
refuse to openly acknowledge a central tenet of public health
— that the state’s responsibility is to look after the health of everyone, which sometimes means guiding or restricting people’s
choices. Their aversion to risk and confrontation has allowed a
parade of misinformed talkers to fill the airwaves and Internet
with wrongheaded theories that, left unchallenged, lead to the
detriment of public health. Rantings about vaccines as a cause
of autism have contributed to a resurgence of measles and
other infectious diseases in areas where vaccination rates have
been low. Manufacturers of sugary and fatty foods and beverages have persisted in marketing campaigns that propel the nation’s obesity problem. And gun makers and their enthusiastic
customers have so far cowed every substantial attempt to limit
the purchase of firearms and ammunition, as U.S. gun-related
SURGEONS GENERAL HAVE ALWAYS HAD TO TAKE ORDERS FROM THEIR POLITICAL BOSSES. What’s changed is deaths continue to surpass 30,000 each year.
A Koop or Elders would have said something about such
that other federal health officials — like the HHS secretary
and the CDC director — have developed an enduring taste shenanigans, and their strong words would undoubtedly
for the bully pulpit, and have come to see surgeons general as have emboldened some lawmakers and policymakers to take
unworthy competitors for it. They have a point: Some sur- action. But the last couple of surgeons general were wimps.
geons general have been quota-filling, just-happy-to-be-here In recent years the bold, speak-truth-to-power public health
appointees with little expertise in influenza or some of the figures in government have resided at the local level. Take
myriad other topics they were expected to speak about to a former New York City Mayor Michael Bloomberg and his
worried public. That was as much a failing of the surgeon city health commissioners, for example, who pushed for
general selection process as of the people who held the office. complete smoking bans, limitations on serving sizes of sugary
In the past decade, in both Republican and Democratic ad- sodas, and a variety of other measures irritating to libertarministrations, surgeons general have become essentially invis- ians and certain corporate interests.
It was William Stewart, the ill-fated surgeon general of
ible. Benjamin’s predecessor, Richard Carmona, was repeatedly
muzzled by the George W. Bush administration, and impor- the late 1960s, who perhaps best described the historical
tant reports he worked on were never allowed to see the light standard for true public health leaders. “From the 1880s
of day. Benjamin had an even lower profile, partly because of onward,” he once said, “the public health movement alhow she was controlled by her bosses and partly because of her ways included rebels: men and women ready to strike out
with new approaches at the roots of evil; crusaders who
own diffidence. ...
There’s no longer a realistic expectation that lawmakers or never lost faith that the movement possessed the breadth
executive branch officials will restore the Office of the Surgeon of vision, as well as the spirit and competence to meet the
General to its past status. In an era of perennial government health needs of a growing and changing society.” Surgeons
budget shortfalls, when local public health departments have general have played that crusader role better and more often
eliminated tens of thousands of jobs — including care-provid- than any other national public health figure. Absent such a
crusader, the public’s health is prey to the misining nurses and outbreak-controlling epidemioloWE
B
E
X
T
RA
formation and self-interest of tobacco companies,
gists — an invisible surgeon general is an indeHear a
snake-oil salesmen and other malefactors. There
fensible waste of money.
conversation with
are other heroes at work, to be sure, some with
But it is also the purpose of this book to
author
Mike Stobbe at
substantial resources and policymaking powers.
mourn what has happened. The weakening of
http://stan.md/1xLtF0G
But the true, traditional leader is missing, and the
the office has led to a vacuum in health policy
fight has suffered as a result. SM
leadership. The federal bureaucrats who have
SO WHAT DOES THE SURGEON GENERAL DO?
At one time, he oversaw nearly all of the federal government’s
civilian health agencies. It was a surgeon general in the 1870s
who resurrected the first federal hospital system. His successors instituted quarantines to fight deadly yellow fever and
cholera epidemics and calmed the nation during the deadly
Spanish flu epidemic of 1918-19. They handled the medical
care of hundreds of thousands of veterans at the end of World
War I, and spearheaded the desegregation of U.S. hospitals
in the 1960s. They also issued warnings to the public about
health dangers ranging from unpasteurized milk to laundry
detergent. Perhaps most famously, Surgeon General Luther
Terry in 1964 released the report that finally settled the question of whether smoking causes lung cancer. Arguably, no
government official has had a greater personal influence on
the public’s health than the U.S. surgeon general.
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S T A N F O R D
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Her left hand
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own experience made me feel it was
OK to get help. It’s a good thing to have
friends.”
STILL AT I T
The goal of the pancreatoduodenectomy, the Whipple procedure, is to remove the head of the pancreas, where
most tumors occur. Because the pancreas is so integrated with other organs,
the surgeon must also remove the first
part of the small intestine (duodenum),
the gallbladder, the end of the common
bile duct and sometimes a portion of the
stomach. The Whipple procedure is a
difficult and demanding operation for
both the person undergoing surgery
and the surgeon. — MAYOCLINIC.ORG
ONLINE DEFINITION
At 11:30 a.m., two hours into surgery,
Wren’s hands are in constant motion inside her patient’s abdomen, cutting, suturing, mopping up blood with pads of
gauze.
“We’re going to start seeing the vena
cava soon,” she tells her excited students.
She’s singing along softly with the
Grateful Dead song playing from her
iPhone.
“Truckin’, got my chips cashed in.
Keep truckin’, like the do-dah man.
Together, more or less in line, just keep
truckin’ on....”
Her hands continue their tour inside
the patient’s body, until they find what
they are searching for: the pancreas, hidden deep inside the abdomen.
“Damn it, I love it when anatomy
works,” she says. She holds the stillattached pancreas gently in both gloved
hands, passing it around for the outstretched fingers to feel the life-threatening tumor embedded there.
“It’s a gigantic rockasaurus,” she says.
“Oh my gosh!” says one of the residents.
“Now will be the decision-making
time,” Wren says. “Now we are going to decide whether we do this bad
S T A N F O R D
M E D I C I N E
boy.” The tumor has grown around a
vein, making it both difficult and dangerous to remove. The four hours of
surgery up to this point have all been
prep work to determine if the tumor
is operable. Now it’s time to decide
whether they will be able to save the
patient’s life. Wren, of course, makes
the decision.
It’s a go.
The hands on the clock move from 1
p.m. to 2 p.m. to 3 p.m. The surgeons
cut and sew. Cut and sew. One of the tiny
cut veins suddenly spurts blood across
the surgeons’ faces.
“Jesus!” Wren says, looking around
at her students. “You can’t flinch. You’ve
got to learn how to sew while your face
gets splashed.”
As the hours pass, Wren’s left hand
continues to work. It holds back the intestines with a pair of large, metal forceps
while the chief resident cuts and sews.
And holds. And holds. Five minutes
stretch into 10, stretch into 15. Finally,
the chief resident ties off the suture and
Wren’s left hand can relax.
She grimaces and shakes out the
cramping hand.
“Is it still bothering you?” someone
says.
“Still not enough nerve innervation,”
she says. Then shrugging, she gets back
to work.
“Now let’s get this tumor out.”
During this eight-hour-long Whipple
surgery in March 2014, Wren’s left hand
cramps only once. The tumor is successfully removed. Now she’s left to worry
about her patient’s recovery.
A NEW LIFE
The Whipple is back to being a routine
procedure for Wren. Six months after
waking up partially paralyzed in June
2012, she was back at it. The following month, she bought all new dive
equipment to replace what she had
lost at the bottom of the South China
Sea. She wasn’t yet strong enough to
put it on herself, but seven months
after that — August 2013 — she was
back deep-sea diving with Maxwell
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2 0 1 4
and swimming with the whale sharks
of Indonesia.
“Everyone thought I was crazy,”
Wren says. Her first question when she
boarded the diving boat was, “Does the
captain speak English?”
Life is different for her today, two
years after her paralysis. She’s lost
some extension and flexion in her neck.
Her left hand isn’t as strong as it once
was. But she can tip her head back in
the shower to wash her own hair. For
that, and so much more, she is grateful.
“I learned some important lessons,”
she says. “One is that confidence is not
something you can pick up off of a store
shelf.” In the past, she had told many of
her students that they just needed more
confidence to be good surgeons. At the
time, she had no idea how difficult it
could be to get that confidence. She had
never experienced what it was like not
to have it.
“As a teacher of surgery, I will never
tell another student that you just need
more confidence.”
The journey to return to surgery has
made her both a better physician and a
better teacher, she says. She understands
better what her patients want. She knows
better what her students need.
She thought long and hard before
deciding to tell her story to others
but ultimately decided that maybe
someone else could learn from her
experience, says Wren, always the
teacher.
“This was a real life test for me,”
she says. “I truly understand now,
there always can be unexpected complications.” SM
— Contact Tracie White at traciew@
stanford.edu
Q&A
A conversation with CNN’s Sanjay Gupta
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Just Say Hello, obviously, is not an
answer to the problem by any means.
But it could be a beginning to an answer. It’s saying, “Look, I want to help.
I know somebody at my workplace or
4 9
my apartment building who is that guy GUPTA : Whether it’s Haiti, Japan after the
or gal who is lonely.” Reaching out in tsunami or an earthquake in Pakistan, I
some way could help set their lives on a think a lot of times it’s just getting out of
different trajectory.
the way of the camera. Pointing things
COS T ELLO : As you travel around the globe
out for people to see and draw their atare there universal questions you’re tention to, but not over-reporting.
asked about medicine, health care or the
There is a desire for me to reinforce
human condition?
the point that what is happening here is
G U P TA: I think the thing that ties us tonot so different from what could hapgether is our quest for good health. Most pen where you are. I think health more
everyone wants to do good by their bod- than anything else serves as a common
ies, understand health, understand how denominator for that. People want good
they could improve the health of their health. They also understand when
family. I think the desire for good health people have been injured and they don’t
and the desire for improved function is have access to health. They may not be
pretty universal.
able to identify Damascus on a map but
COS T ELLO : In addition to a career as a
if I explain to them that when the bombs
physician, why did you want to be a jour- came raining down, the same family that
nalist and storyteller? had been driving their kids to school the
G U P TA: I always liked to tell stories. That’s
day before, grocery shopping after that,
what my parents and friends
stopping at a bank to withdraw
say. I wasn’t the best student
some money from an ATM,
WE B E X T RA
when I was younger. One of the
that they are now fleeing with
Hear the
conversation
tricks I learned as a student that
whatever few possessions they
at http://stan.md/
carried me through medical
could gather and running for
1u9MCFQ
school was to really understand
the border, that’s a family like a
the stories behind things. Even
lot of families in your neighborwhen I was in medical school studying hood. If they feel more compassionate,
biological chemistry, understanding the more compelled in some way, that’s what’s
stories behind the people who had made really important to me as a reporter.
This interview was condensed and
interesting discoveries and why they
edited by Paul Costello.
made those discoveries made it stick in
my brain. I just like stories. I was a voracious reader. I remain somebody who
likes to read all sorts of different topics. F E A T U R E
When I started writing, I felt it was a Sculpting bones
strength and just ran to it.
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COS T ELLO : It’s well-known you had talks
The greater challenge was cleaning the
with President Obama about being sur- pin sites, which needed to be done at
geon general and turned it down. As you least every other day. “It was extremely
look down the road, do you see yourself painful,” says Suki, “far worse than adin public service?
justing the struts.” The frame’s size was
G U P TA: I worked in the White House
also somewhat cumbersome, causing
— in the Clinton administration. My in- some bumps and bruises on her healthy
terest at the time was in public service. leg, sometimes on other people’s legs,
I could absolutely see myself doing it and often bringing unwelcome stares
again. The timing for the surgeon gen- from other children.
eral job wasn’t right for me. I would have
“It was draconian-looking,” says
had to give up my job as a neurosurgeon, Greg, “and horrible to imagine what it
which I found quite ironic.
was doing to her leg. But it was also magCOS T ELLO : When you parachute into
nificent, extending her leg and bringing
disasters around the globe what do you her foot forward in one operation.”
look for to tell a compelling story?
For Young, the frame stands alone as
5 0
S U M M E R
an ideal tool for healing his pediatric patients. “I really like how the technology
allows me to basically sculpt the bone,”
he says. “It’s the perfect blend of engineering and art.”
THE TECHNIQUE WAS DISCOVERED BY
more than 60 years ago, by a
doctor working alone in a remote province of Siberia, Russia.
In Limb Lengthening and Reconstruction Surgery — a textbook for
orthopaedic surgeons practicing this
approach — Svetlana Ilizarov, MD,
tells the story of her father’s discovery.
Gavriil Ilizarov, MD, PhD, started out
as a general practitioner, but learned
orthopaedic surgery by necessity as
the only doctor in an area “the size
of a small European country.” For his
patients, many of whom were Russian
soldiers returning from World War II
with a variety of bone injuries, he developed a new type of external fixator
device. Unlike previous models, his
completely encircled the limb, with
parallel bars screwed to rings above
and below the break. By tightening the
bars on the fixator, bones with missing
fragments or gaps could be healed using grafted bone and compression to
encourage the pieces of bone to fuse
back together. Just as Giana would decades later, and as the majority of patients using an external fixator still do,
Ilizarov’s patients were also responsible
for adjusting the screws on the fixator
— only their job was to tighten, not
lengthen, the screws to increase compression until the bone healed.
On one occasion in the early 1950s,
a patient turned the screws in the wrong
direction, separating the bone pieces
instead of closing them, writes Svetlana
Ilizarov. Her father was shocked to find
that new bone had grown in the gap. This
accidental discovery led to his method of
distraction osteogenesis, through which
non-healing fractures could be corrected, deformed limbs straightened and
uneven limbs lengthened. Only muscles
and tendons — which can stretch only so
far — set the limits.
CHANCE
2 0 1 4
S T A N F O R D
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“The Ilizarov method … revolutionized the process of deformity correction,” writes Svetlana.
Ilizarov’s method did not reach the
United States until the late 1980s.
When it did, two early adopters,
Charles Taylor, MD, an orthopaedic
surgeon in Memphis, Tenn., and his
brother, Harold Taylor, an engineer,
redesigned it. In the early 1990s, they
replaced the long, parallel bars that
ADJUSTING TO
A TAYLOR
SPATIAL FRAME
TIPS FROM G IANA
1. When first getting the frame:
“It’s kind of hard at first, but you’ll
get used to it. It’s a little scary, but
you’ll be fine if you’re brave.”
2. “Take your clothes and get snaps
put in them.”
3. When sleeping: “Put a pillow
under your foot so it doesn’t just
hang there.”
4. When taking your first step:
“Start with the foot without the
brace and take your brace foot and
try a little weight at first.”
5. “Turning the struts was painful
and scary. Turning them myself
made it easier because I could stop
when it hurt and start again after I
took a break.”
6. Dealing with pain: “If you’re having a hard time dealing with your
pain, just take a few deep breaths
and it will feel better.” screwed into the frame with hinged
struts that could change length like a
telescope, one end fitting inside the
other. They set the struts at angles to
each other, making three triangular
formations that encircled the limb in a
zigzag. Each strut could be adjusted individually, allowing complete flexibility
of the rings in relation to each other,
with no equipment changes required
during healing.
The new design also greatly increased
S T A N F O R D
M E D I C I N E
the complexity of the device’s settings.
So, with the new Taylor Spatial Frame
came a computer program that used the
exact settings planned before surgery to
generate a prescription for correction in
the weeks or months following surgery.
“The computer program is mathematically accurate to within a millionth of an
inch and a ten-thousandth of a degree,”
writes Charles Taylor in Limb Lengthening and Reconstruction.
Stanford’s Young, who was first introduced to the device during his residency
at Northwestern Memorial Hospital,
has also used the frame to treat patients
during orthopaedic medical missions in
Nicaragua and Haiti. “The computerized prescription sits on the spatial frame
website, so it provides the ability to share
cases and adjust prescriptions remotely,”
he says.
In October 2013, Young removed the
frame on Giana’s foot. Physical therapy
helped her get her ankle back in motion
again. Then, on Valentine’s Day 2014,
with her left leg lengthened by close
to 3 inches and rotated so that her foot
was aligned, Giana’s spatial frame was
removed and a cast was put on for one
month. From the cast, she graduated to
a boot, which she could remove at night
— a welcome relief.
Giana will need to be assessed again
when she’s in her early teens, and her left
leg may need further lengthening if it
continues to grow at a slower pace than
her right. Because the fragility caused by
her rare bone disease will continue, she’ll
need to steer clear of the highest impact
activities like gymnastics or soccer, but
still has a lot to look forward to.
“I want to do cannonballs into the
water,” Giana says. “I want to climb up
onto the play structure and swing from
the monkey bars and run and play tag.
I want to go to the beach — that’s what
I want to do most of all.” And now that
her leg is healed enough that there’s no
risk of sand getting into the wounds
left by the pins, that’s exactly what she’s
ready to do. SM
S U M M E R
— Contact Julie Greicius at jgreicius@
stanfordchildrens.org
2 0 1 4
F E AT U R E
Healing wounds
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O U TS I D E H E L P
It isn’t just physicians who are taking up
the challenge of helping wounds heal.
Interdisciplinary teams of engineers,
chemists and other specialists are also
creating new technologies to help skin
that can’t readily heal itself.
At Vanderbilt University in Tennessee, Craig Duvall, PhD, an assistant
professor of biomedical engineering,
is taking an approach that could be
called “the enemy of my enemy is a
friend” technique. He collaborated with
chemical engineers and a pathologist
to develop a spongy scaffold filled with
small molecules that order wound-area
cells to shut down production of an enzyme that blocks blood vessel growth in
chronic wounds.
In normal wound healing, a molecule called HIF1-alpha helps trigger
the growth of blood vessels when there
isn’t enough oxygen getting to cells. But
HIF1-alpha is thwarted in the oxygendepleted tissue of chronic wounds by an
enzyme called PHD2. With fewer blood
vessels, the skin defect is left without a
way to get the repair factors and cells that
it needs to heal.
When Duvall injects the foamy scaffold onto wounds, a steady trickle of
small interfering RNA molecules work
their way into wound cells and stop
PHD2 production, giving HIF1-alpha
a chance to go back to work and help
blood vessels sprout again. “We stop
the negative feedback loop that impedes
wound healing,” says Duvall.
Someday, scientists might just print a
new patch of tissue to heal those wounds.
A Harvard University team led by materials engineer Jennifer Lewis, PhD, took
the first step by printing a three-dimensional tissue scaffold — complete with
blood vessels.
Lewis and her colleagues used a 3-D
bioprinter, a hulking custom-built machine that resembles a 2-ton version of
5 1
an old-fashioned laser printer. The printer uses four “inks” that progressively layer a silicone-based outer border, an inner
matrix with two kinds of skin cells called
fibroblasts, and an interwoven vascular
network that can be lined with living
cells, to create three-dimensional tissues.
“We’re nowhere near the goal of
making fully functional living tissue,”
says Lewis. “But these vascularized tissue constructs represent a foundational
step.” As a materials scientist, Lewis says
it was a grand challenge to apply her
background to create living things. Although she’s creating a new kind of toolbox, she’s quick to point out that scientific advances like this take expertise “on
both sides of the aisle.”
P REV EN T I ON
IS THE BEST M ED I C I N E
Improved methods for healing wounds
would be wonderful, but preventing
them would be even better. Along with
other Stanford scientists, Gurtner is
working to stop diabetic ulcers from developing in the first place. His group is
repurposing a drug called deferoxamine,
or DFO, already approved by the Food
and Drug Administration for treating
diseases that cause a toxic overload of
iron in the blood. When a DFO-treated
bandage is applied to the at-risk skin on a
diabetic’s foot, it improves the skin condition — making it thicker and maintaining blood vessel growth.
But more research trials are needed
before these new treatments are prescribed for patients. “Ultimately, the answers will be found in the clinics,” says
Gurtner. It will be easier to get those
answers at Stanford’s new wound center.
“Patients are realizing that wound
care is very specialized,” says Subhro
Sen, MD, clinical assistant professor
of plastic and reconstructive surgery
and co-director of the new center.
When people cut a finger, they head
for an emergency room or their primary care doctors. But if treatment is
needed for chronic wounds, patients
end up seeing a number of different specialists. “Now we’ll be able to
5 2
give focused, multidisciplinary care.
Instead of making multiple appointments at separate locations to see surgeons, get tests and consult with other
specialists, patients can get that care
all under one roof.”
That’s something Kaufman says he
would have appreciated when he was
making three-hour round trips from
his home in Dublin, Calif., to see Dalman and the other doctors on his team
at Stanford, plus twice-weekly journeys
for hyperbaric oxygen therapy even farther afield. And while he’s happy that
Stanford’s getting a wound treatment
center, he’s hoping not to visit anytime soon. Wound-free for almost two
years, Kaufman would rather spend his
time taking long trips with his wife —
like the round-the-world journey he
was recently able to make, taking in the
sights on his own two feet. SM
— Contact Elizabeth Devitt at
[email protected]
F E AT U R E
sciousness comes from basic human curiosity: What makes us tick? What makes
you have a different view on the world
than me? Can we download someone’s
memories from their brain? But there
are also more practical questions that
the science can lend a hand in answering: How can we measure consciousness
in patients who appear to be in comas?
How can we develop better anesthetics?
“What I’m always hoping is that hearing about this kind of work makes people
ask more questions about what it means
when they themselves enter different
states,” says Chander. She challenges
people to pay attention to what’s happening in their brain when their state of
attention, or awareness about the world
around them, changes.
“Some people still think consciousness can’t be accessed by scientific methods,” says Parvizi. “But that’s a very unfortunate view.” Scientists are already
there, he says, getting at the heart of
consciousness every day. SM
— Contact Sarah C.P. Williams at
[email protected]
Going under
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conscious than people sleep-walking.
Determining how to comparatively measure such different states of awakeness
and awareness in the brain would give
scientists an unprecedented look into
what it means for a person to be a living
human being.
Some philosophers, Churchland says,
remain skeptical that consciousness can
be gauged in such a concrete, physical
way. But she prefers to think about the
limits of science to study consciousness
as a known unknown. “We cannot be
sure whether we’re up against a solvable
or an unsolvable problem,” she says. “But
when philosophers claim we’ll never understand the brain basis of consciousness, they are making a rash prediction
about the future of science. Against that
prediction is the significant progress that
has already been made. The fact is, the
naysayers cannot really know what science will discover.”
Much of the drive to understand con-
S U M M E R
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Rethinking Alzheimer’s
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Long-slumbering synapse-scouring
pathways can be awakened by those
inflammatory signals, causing massive synapse loss akin to “a fire burning through the brain,” he says.
Annexion, a startup biotechnology company co-founded by Barres, is
already making drugs that selectively
and powerfully target elements of the
complement cascade. Barres has high
hopes. “I believe that drugs that block
the complement cascade may not only
stop neurodegeneration in Alzheimer’s
— and, perhaps, other neurodegenerative disorders — but may buy time to
allow the brain to repair lost synapses,
quite possibly restoring lost neurological function.” Time will tell. Annexion
is actively raising money to finance
early-stage, proof-of-principle clinical
trials of the new drugs, beginning with
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patients who have other, easier-to-track
neurodegenerative diseases.
MORE SC R UT I N Y OF
THE BRA IN’S I M M UN E C EL L S
In their day-to-day life, microglia are beat
cops. Among their many roles beyond secreting C1q, one is devouring odd bits of
circulating glop or suspended intercellular
debris. • Tony Wyss-Coray, PhD, a professor of neurology and neurological sciences, has shown that defects in microglial glop-gobbling capabilities can impair
their ability to gobble up early-stage Abeta accumulations, resulting in a buildup
of A-beta in aging brains. One rare mutation causing such a defect is known to
triple or quadruple Alzheimer’s disease
risk. When Wyss-Coray’s team compared
autopsied brains from five Alzheimer’s
patients and five people who had died of
other causes, they found that microglia in
the Alzheimer’s patients’ brains were riddled with precisely those A-beta-ingesting
defects his group had identified.
Even healthy microglia have angermanagement issues. When chronically
hyperactivated, as for example occurs in
the chronic presence of excessive A-beta,
they get stuck in overdrive, squirting out
inflammatory substances that can have
deleterious effects on brain cells. They
also lose their ability to clear the offending A-beta or other toxic substances, generating a destructive inflammatory vicious
circle. Katrin Andreasson, MD, professor
of neurology and neurological sciences,
recently identified a new way of selectively
soothing microglial cells, thus halting the
cycle of violence and potentially quenching that synapse-destroying “fire burning
through the brain” that inflammatory
mechanisms appear to induce. She’s continuing this research and hopes the work
leads to better anti-inflammatory drugs.
GOOD NEWS FOR OL D BR A I N S?
In the end, Alzheimer’s is above all a disease of old age. Some time ago, WyssCoray’s group discovered that something
— they weren’t sure what — in the blood
of old mice messed up new nerve-cell
production and cognitive performance
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in young mice, and they suspected that
young mice’s blood might have a beneficial effect on old brains. In a recently
published study in Nature Medicine,
Wyss-Coray and his colleagues showed
just that. Not only did old mice whose
bloodstreams were experimentally interknit with those of young mice exhibit
numerous positive neurophysiological changes, but regular old mice given
blood plasma from young mice got better at tests of spatial learning, memory
and other cognitive functions.
“Exposure to young blood late in
life,” Wyss-Coray says, “is capable of
rejuvenating an old brain’s nerve-cell
function and behavioral performance.”
He’s bent on learning what it is in young
blood that is recharging the brain. Isolating that factor, or those factors, could
lead to pharmacological methods of
preventing or delaying the onset of
Alzheimer’s in aging people (and that’s
all of us). But meanwhile, he’s not waiting around. He’s started a biotechnology company, called Alkahest, to speed
the initiation of clinical trials in which
Alzheimer’s patients will receive infusions of young donors’ blood and be
monitored via brain imaging, standard
neuropsychological tests and interviews
with patients and caregivers to see if the
treatment provides any benefit.
Longo’s group has pioneered the development of small-molecule drugs that
target the same receptors used by much
bulkier growth-factor proteins involved
in restoring nerve cells frayed by conditions such as Alzheimer’s. In animal
models, these molecules counteract a
number of key Alzheimer degenerative
mechanisms, including inflammatory
processes, and can restore the loss of
synaptic connections in mouse models
of late-stage Alzheimer’s disease. One
of these compounds has made the rare
leap from mouse to human studies and
is in early-phase clinical trials sponsored
by PharmatrophiX, a company Longo
founded before coming to Stanford.
He says he will be happy to see the
success of any or all of these diagnostic and therapeutic approaches, most
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of them geared toward discovering and
treating the disease before symptoms get
too advanced. And he is particularly happy that his team’s compounds can reverse
synapse loss in mice. “We need drugs like
this,” he says. “Even if we could stop new
Alzheimer’s cases in their tracks, there
will always be patients walking in who already have severe symptoms. And I don’t
think they should be forgotten.” SM
— Contact Bruce Goldman at
[email protected]
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GLOBAL EYE
G AT H E R I N G M E D I C A L N E W S F R O M A R O U N D T H E WO R L D
On a Thursday this spring I was sitting at my desk at NBC News in New York City.
By Friday, I was walking through the squalor and mud of a Syrian refugee camp
in Lebanon with the chief medical editor for NBC News, Nancy Snyderman, MD.
• I am a fourth-year medical student — but as the Stanford-NBC News Fellow in
Global Health and Media I’m getting exposure to global health and medical journalism. • Already since last summer, I’ve worked in Haiti at a hospital, in New Delhi as an intern for the World
Health Organization and in Thailand to help with an international summit on leprosy. I spent the fall at Stanford’s
graduate program in journalism. I have interviewed a mind-boggling array of people: a man with leprosy in India,
the president of the American Academy of Dermatology, illegal immigrants living in a Northern California garage,
a California state senator, countless medical researchers at the cutting edge of their fields.
• And for a week in March I found myself at the refugee camp in Lebanon, following the
stories of Syrian children living there in tents with their entire families on the bank of a
trash-filled river. I interviewed the kids — about their toys, their squabbles, their memories
of Syria and their hopes for the future. One girl, 7, with piercing blue eyes, became my
shadow and my companion. At one point she leaned over to whisper something in my ear.
When I asked her to tell the translator, she shook her head. “She’s telling me that what she
wants to say is between you and her only,” he informed me. I could only smile back at her.
That chilly, rainy week I saw birth, death, laughter and tears. I am used to seeing those
things through a medical caregiver’s lens, but not through a journalist’s. My job was not to
intervene, but to observe, document and report.
One unforgettable story was that of 19-month-old Nevine, who arrived with her right side paralyzed. Doctors
were worried — justifiably — about polio. Syria’s vaccination rates have plummeted: from 99 percent before the
war to 52 percent in 2012. When Nevine’s mother looked at me with pain in her eyes and asked whether her child
would ever walk again, I wanted nothing more than to offer her assurances — but I couldn’t. In journalism and in
medicine, it’s important not to jump to conclusions.
One lesson I learned is that, consciously or not, physicians always function as health-care reporters. We are
cast in this role when we interpret data for our patients, recommend certain interventions or review information
patients have printed from WebMD. Doctors know firsthand what an honor it is to be with people at their most
vulnerable and listen to their stories.
Sometimes those stories have happy endings. We later found out that Nevine’s test results were not consistent
with polio. An MRI showed a small area of bleeding deep in the part of her brain that controls movement on the
right side of her body. By the time I left, she was already improving. —
H AYL E Y GOL DB AC H
HAYL EY GOLDB ACH
Children play
on the outskirts
of a Syrian refugee
camp in Lebanon’s
Bekaa Valley.
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Sea lion seizures
ILLNESS PROVIDES INSIGHT INTO EPILEPSY
In the first four months of this year, 40 sea lions turned up on Northern California shores
both sides of the brain. The ailing sea
suffering from seizures caused by a neurotoxin found in algae. That’s 13 more of the
lions also showed a pattern of nerve cell
animals than last year during the same period and more than double in previous years. The
reorganization in the brain matching that
sea lions had been feeding on small fish contaminated with domoic acid, a toxin that has
of humans with epilepsy.
blooms on the coast.
Since 1998, the Marine Mammal Center
in Sausalito, Calif., has rescued a few
A recent study led by Stanford
hundred sea lions with epilepsy every year.
scientists characterized the brain damage
And while anticonvulsive drugs can help
caused by this toxin. What they found
control symptoms in both species, the
could lead to better therapies not only
disease has no cure.
for the pinnipeds but also for humans.
Buckmaster has been collaborating on
Paul Buckmaster, PhD, DVM, a pro-
the project with the marine center for the last
fessor of comparative medicine, and
four years and continues to study the brains
his colleagues examined the brains of the affected sea mammals and found a pattern of
of those animals that are beyond rescue.
damage in the hippocampus — the brain’s memory center — similar to that in humans
“What we need is an interventional
with temporal lobe epilepsy, one of the most common forms of the disease. The animals
treatment — both in humans and sea
had lost 50 percent of the neurons in the hippocampus, with the damage occurring on just
lions,” Buckmaster says. “You’d give the
one side of the brain.
treatment right after the brain injury, and
“That was really surprising,” says Buckmaster, a veterinarian specializing in epilepsy.
that would prevent them from developing
“That is what you find in people — 80 percent of the time the damage is just on one
epilepsy. That’s the dream, but we are not
side.” In rodents, the animals typically used in epilepsy studies, damage appears on
there yet.” —
R U TH ANN R I C H TE R
T O S UB S C RIB E
T O S TAN F OR D M EDIC INE
e-mail [email protected]
or call (650) 723-6911.
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increased along with the growth in algae